Out-of-hospital cardiac arrest in children in Norway: A national cohort study, 2016-2021.

Aim: Children constitute an important and distinct subgroup of out-of-hospital cardiac arrest (OHCA) patients. This population-based cohort study aims to establish current age-specific population incidence, precipitating causes, circumstances, and outcome of paediatric OHCA, to guide a focused approach to prevention and intervention to improve outcomes. Methods: Data from the national Norwegian Cardiac Arrest Registry was extracted for the six-year period 2016-21 for persons aged <18 years. We present descriptive statistics for the population, resuscitation events, presumed causes, treatment, and outcomes, alongside age-specific incidence and total paediatric mortality rates. Results: Three hundred and eight children were included. The incidence of OHCA was 4.6 per 100 000 child-years and markedly higher in children <1 year at 20.9 child-years. Leading causes were choking, cardiac and respiratory disease, and sudden infant death syndrome. Overall, 21% survived to 30 days and 18% to one year. Conclusion: A registry-based approach enabled this study to delineate the characteristics and trajectories of OHCA events in a national cohort of children. Precipitating causes of paediatric OHCA are diverse compared to adults. Infants aged <1 year are at particularly high risk. Mortality is high, albeit lower than for adults in Norway. A rational community approach to prevention and treatment may focus on general infant care, immediate first aid by caretakers, and identification of vulnerable children by primary health providers. Cardiac arrest registries are a key source of knowledge essential for quality improvement and research into cardiac arrest in childhood.

New, simplified versus standard photodynamic therapy (PDT) regimen for superficial and nodular basal cell carcinoma (BCC): A single-blind, non-inferiority, randomised controlled multicentre study.

BACKGROUND: Topical photodynamic therapy (PDT) is an approved and widely used treatment for low-risk basal cell carcinoma (BCC), comprising two sessions with an interval of 1 week. Simplification of the treatment course can be cost-effective, easier to organize, and cause less discomfort for the patients. METHODS AND FINDINGS: We performed an investigator-initiated, single-blind, non-inferiority, randomized controlled multicentre study with the objective of investigating whether a simpler and more flexible PDT regimen was not >10% less effective than the standard double PDT in the treatment of primary, superficial, and nodular ≤2 mm-thick BCC and evaluate the cosmetic outcome. With a non-inferiority margin of 0.1 and an expected probability complete response of 0.85, 190 tumours were required in each group. Histologically verified BCCs from seven centres in Norway were randomly assigned (1:1) to either receive a new regimen of single PDT with one possible re-treatment of non-complete responding tumours, or the standard regimen. The primary endpoint was the number of tumours with complete response or treatment failure at 36 months of follow-up, assessed by investigators blinded to the treatment regimen. Intention-to-treat and per-protocol analyses were performed. The cosmetic outcome was recorded. The study was registered with ClinicalTrials.gov, NCT-01482104, and EudraCT, 2011-004797-28. A total of 402 BCCs in 246 patients were included; 209 tumours assigned to the new and 193 to the standard regimen. After 36 months, there were 61 treatment failures with the new and 34 failures with the standard regimen. Complete response rate was 69.5% in the new and 81.1% in the standard treatment group. The difference was 11.6% (upper 97.5% CI 20.3), i.e. > than the non-inferiority margin of 10%. Cosmetic outcomes were excellent or good in 92% and 89% following the new and standard regimens, respectively. CONCLUSIONS: Single PDT with possible re-treatment of primary, superficial, and nodular ≤ 2-mm-thick BCC was significantly less effective than the approved standard double treatment. The cosmetic outcome was favorable and comparable between the two treatment groups.

Machine learning model to predict evolution of pulseless electrical activity during in-hospital cardiac arrest.

Background: During pulseless electrical activity (PEA) the cardiac mechanical and electrical functions are dissociated, a phenomenon occurring in 25-42% of in-hospital cardiac arrest (IHCA) cases. Accurate evaluation of the likelihood of a PEA patient transitioning to return of spontaneous circulation (ROSC) may be vital for the successful resuscitation. The aim: We sought to develop a model to automatically discriminate between PEA rhythms with favorable and unfavorable evolution to ROSC. Methods: A dataset of 190 patients, 120 with ROSC, were acquired with defibrillators from different vendors in three hospitals. The ECG and the transthoracic impedance (TTI) signal were processed to compute 16 waveform features. Logistic regression models where designed integrating both automated features and characteristics annotated in the QRS to identify PEAs with better prognosis leading to ROSC. Cross validation techniques were applied, both patient-specific and stratified, to evaluate the performance of the algorithm. Results: The best model consisted in a three feature algorithm that exhibited median (interquartile range) Area Under the Curve/Balanced accuracy/Sensitivity/Specificity of 80.3(9.9)/75.6(8.0)/ 77.4(15.2)/72.3(16.4) %, respectively. Conclusions: Information hidden in the waveforms of the ECG and TTI signals, along with QRS complex features, can predict the progression of PEA. Automated methods as the one proposed in this study, could contribute to assist in the targeted treatment of PEA in IHCA.

Extracting physiologic and clinical data from defibrillators for research purposes to improve treatment for patients in cardiac arrest.

Background: A defibrillator should be connected to all patients receiving cardiopulmonary resuscitation (CPR) to allow early defibrillation. The defibrillator will collect signal data such as the electrocardiogram (ECG), thoracic impedance and end-tidal CO2, which allows for research on how patients demonstrate different responses to CPR. The aim of this review is to give an overview of methodological challenges and opportunities in using defibrillator data for research. Methods: The successful collection of defibrillator files has several challenges. There is no scientific standard on how to store such data, which have resulted in several proprietary industrial solutions. The data needs to be exported to a software environment where signal filtering and classifications of ECG rhythms can be performed. This may be automated using different algorithms and artificial intelligence (AI). The patient can be classified being in ventricular fibrillation or -tachycardia, asystole, pulseless electrical activity or having obtained return of spontaneous circulation. How this dynamic response is time-dependent and related to covariates can be handled in several ways. These include Aalen's linear model, Weibull regression and joint models. Conclusions: The vast amount of signal data from defibrillator represents promising opportunities for the use of AI and statistical analysis to assess patient response to CPR. This may provide an epidemiologic basis to improve resuscitation guidelines and give more individualized care. We suggest that an international working party is initiated to facilitate a discussion on how open formats for defibrillator data can be accomplished, that obligates industrial partners to further develop their current technological solutions.

Real-time feedback on chest compression efficacy by hands-free carotid Doppler in a porcine model.

Aim: Current guidelines for cardiopulmonary resuscitation (CPR) recommend a one-size-fits-all approach in relation to the positioning of chest compressions. We recently developed RescueDoppler, a hands-free Doppler ultrasound device for continuous monitoring of carotid blood flow velocity during CPR. The aim of the present study is to investigate whether RescueDoppler via real-time hemodynamic feedback, could identify both optimal and suboptimal compression positions. Methods: In this model of animal cardiac arrest, we induced ventricular fibrillation in five domestic pigs. Manual chest compressions were performed for ten seconds at three different positions on the sternum in random order and repeated six times. We analysed Time Average Velocity (TAV) with chest compression position as a fixed effect and animal, position, and sequential time within animals as random effects. Furthermore, we compared TAV to invasive blood pressure from the contralateral carotid artery. Results: We were able to detect changes in TAV when altering positions. The positions with the highest (range 19 to 48 cm/s) and lowest (6-25 cm/s) TAV were identified in all animals, with corresponding peak pressure 50-81 mmHg, and 46-64 mmHg, respectively. Blood flow velocity was, on average, highest at the middle position (TAV 33 cm/s), but with significant variability between animals (SD 2.8) and positions within the same animal (SD 9.3). Conclusion: RescueDoppler detected TAV changes during CPR with alternating chest compression positions, identifying the position yielding maximal TAV. Future clinical studies should investigate if RescueDoppler can be used as a real-time hemodynamical feedback device to guide compression position.

Automatic assessment of left ventricular function for hemodynamic monitoring using artificial intelligence and transesophageal echocardiography.

We have developed a method to automatically assess LV function by measuring mitral annular plane systolic excursion (MAPSE) using artificial intelligence and transesophageal echocardiography (autoMAPSE). Our aim was to evaluate autoMAPSE as an automatic tool for rapid and quantitative assessment of LV function in critical care patients. In this retrospective study, we studied 40 critical care patients immediately after cardiac surgery. First, we recorded a set of echocardiographic data, consisting of three consecutive beats of midesophageal two- and four-chamber views. We then altered the patient's hemodynamics by positioning them in anti-Trendelenburg and repeated the recordings. We measured MAPSE manually and used autoMAPSE in all available heartbeats and in four LV walls. To assess the agreement with manual measurements, we used a modified Bland-Altman analysis. To assess the precision of each method, we calculated the least significant change (LSC). Finally, to assess trending ability, we calculated the concordance rates using a four-quadrant plot. We found that autoMAPSE measured MAPSE in almost every set of two- and four-chamber views (feasibility 95%). It took less than a second to measure and average MAPSE over three heartbeats. AutoMAPSE had a low bias (0.4 mm) and acceptable limits of agreement (- 3.7 to 4.5 mm). AutoMAPSE was more precise than manual measurements if it averaged more heartbeats. AutoMAPSE had acceptable trending ability (concordance rate 81%) during hemodynamic alterations. In conclusion, autoMAPSE is feasible as an automatic tool for rapid and quantitative assessment of LV function, indicating its potential for hemodynamic monitoring.

Non-shockable rhythms: A parametric model for the immediate probability of return of spontaneous circulation.

BACKGROUND: Cardiac arrest can present with asystole, Pulseless Electrical Activity (PEA), or Ventricular Fibrillation/Tachycardia (VF/VT). We investigated the transition intensity of Return of spontaneous circulation (ROSC) from PEA and asystole during in-hospital resuscitation. MATERIALS AND METHODS: We included 770 episodes of cardiac arrest. PEA was defined as ECG with >12 QRS complexes per min, asystole by an isoelectric signal >5 seconds. The observed times of PEA to ROSC transitions were fitted to five different parametric time-to-event models. At values ≤0.1, transition intensities roughly represent next-minute probabilities allowing for direct interpretation. Different entities of PEA and asystole, dependent on whether it was the primary or a secondary rhythm, were included as covariates. RESULTS: The transition intensities to ROSC from primary PEA and PEA after asystole were unimodal with peaks of 0.12 at 3 min and 0.09 at 6 min, respectively. Transition intensities to ROSC from PEA after VF/VT, or following transient ROSC, exhibited high initial values of 0.32 and 0.26 at 3 minutes, respectively, but decreased. The transition intensity to ROSC from initial asystole and asystole after PEA were both about 0.01 and 0.02; while asystole after VF/VT had an intensity to ROSC of 0.15 initially which decreased. The transition intensity from asystole after temporary ROSC was constant at 0.08. CONCLUSION: The immediate probability of ROSC develops differently in PEA and asystole depending on the preceding rhythm and the duration of the resuscitation attempt. This knowledge may aid simple bedside prognostication and electronic resuscitation algorithms for monitors/defibrillators.

Hands-free continuous carotid Doppler ultrasound for detection of the pulse during cardiac arrest in a porcine model.

Background/Purpose: Pulse palpation is an unreliable method for diagnosing cardiac arrest. To address this limitation, continuous hemodynamic monitoring may be a viable solution. Therefore, we developed a novel, hands-free Doppler system, RescueDoppler, to detect the pulse continuously in the carotid artery. Methods: In twelve pigs, we evaluated RescueDopplers potential to measure blood flow velocity in three situations where pulse palpation of the carotid artery was insufficient: (1) systolic blood pressure below 60 mmHg, (2) ventricular fibrillation (VF) and (3) pulseless electrical activity (PEA). (1) Low blood pressure was induced using a Fogarty balloon catheter to occlude the inferior vena cava. (2) An implantable cardioverter-defibrillator induced VF. (3) Myocardial infarction after microembolization of the left coronary artery caused True-PEA. Invasive blood pressure was measured in the contralateral carotid artery. Time-averaged blood flow velocity (TAV) in the carotid artery was related to mean arterial pressure (MAP) in a linear mixed model. Results: RescueDoppler identified pulsatile blood flow in 41/41 events with systolic blood pressure below 60 mmHg, with lowest blood pressure of 19 mmHg. In addition the absence of spontaneous circulation was identified in 21/21 VF events and true PEA in 2/2 events. The intraclass correlation coefficient within animals for TAV and MAP was 0.94 (95% CI. 0.85-0.98). Conclusions: In a porcine model, RescueDoppler reliably identified pulsative blood flow with blood pressures below 60 mmHg. During VF and PEA, circulatory arrest was rapidly and accurately demonstrated. RescueDoppler could potentially replace unreliable pulse palpation during cardiac arrest and cardiopulmonary resuscitation.

Did lockdown influence bystanders' willingness to perform cardiopulmonary resuscitation? A worldwide registry-based perspective.

AIM: Bystander cardiopulmonary resuscitation (CPR) significantly increases the survival rate after out-of-hospital cardiac arrest. Using population-based registries, we investigated the impact of lockdown due to Covid-19 on the provision of bystander CPR, taking background changes over time into consideration. METHODS: Using a registry network, we invited all registries capable of delivering data from 1. January 2017 to 31. December 2020 to participate in this study. We used negative binominal regression for the analysis of the overall results. We also calculated the rates for bystander CPR. For every participating registry, we analysed the incidence per 100000 inhabitants of bystander CPR and EMS-treated patients using Poisson regression, including time trends. RESULTS: Twenty-six established OHCA registries reported 742 923 cardiac arrest patients over a four-year period covering 1.3 billion person-years. We found large variations in the reported incidence between and within continents. There was an increase in the incidence of bystander CPR of almost 5% per year. The lockdown in March/April 2020 did not impact this trend. The increase in the rate of bystander CPR was also seen when analysing data on a continental level. We found large variations in incidence of bystander CPR before and after lockdown when analysing data on a registry level. CONCLUSION: There was a steady increase in bystander CPR from 2017 to 2020, not associated with an increase in the number of ambulance-treated cardiac arrest patients. We did not find an association between lockdown and bystanders' willingness to start CPR before ambulance arrival, but we found inconsistent patterns of changes between registries.

A Web-Based Communication Tool for Postoperative Follow-up and Pain Assessment at Home After Primary Knee Arthroplasty: Feasibility and Usability Study.

BACKGROUND: We report the use of an electronic tool, Eir (Eir Solutions AS, Norway), for symptom registration at home after knee arthroplasty. This electronic tool was used in a randomized controlled trial (RCT) comparing 3 different analgesic regimens with respect to postoperative pain and side effects. OBJECTIVE: The aim of this substudy was to investigate this electronic tool for symptom registrations at home with respect to usability (ie, how easy it was to use) and feasibility (ie, how well the tool served its purpose). METHODS: To assess the tool's usability, all participants were invited to fill out the 10-item System Usability Scale (SUS) after using the tool for 8 days. To assess feasibility, data regarding the participants' ability to use the tool with or without assistance or reminders were collected qualitatively on a daily basis during the study period. RESULTS: A total of 134 patients completed the RCT. Data concerning feasibility of the web-based tool were collected from all 134 patients. The SUS was completed by 119 of the 134 patients; 70.2% (94/134) of the patients managed to use the tool at home without any technical support. All technical challenges were related to the login procedure or internet access. The mean SUS score was 89.6 (median 92.5; range 22.5-100). CONCLUSIONS: This study showed high feasibility and high usability of the Eir web tool. The received reports gave the necessary information needed for both research data and clinical follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT02604446; https://www.clinicaltrials.gov/ct2/show/NCT02604446.

Metformin serum concentrations during pregnancy and post partum - A clinical study in patients with polycystic ovary syndrome.

BACKGROUND AND OBJECTIVES: Metformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of metformin. The aim of this study was to explore the time course of the pregnancy-related changes in metformin pharmacokinetics and the return to the non-pregnant state. METHOD: A subgroup of women in the PregMet2 study (n = 73) agreed to provide serum samples at three time-points in pregnancy (gestational weeks 19, 28 and 32) and once in post partum, (either 2, 4 or 8 weeks after delivery). Serum metformin concentrations were compared using a four-parameter logistic model. FINDINGS: The mean steady-state serum concentration of metformin during pregnancy was 9.39 µmoL/L, whereas the post partum concentration was 12.36 µmoL/L, an increase of 32% (p = 0,019). This change took place already during the first 2 weeks post partum. CONCLUSION: Clinicians who treat pregnant women with metformin should be aware of the significant decrease in metformin concentration mediated by pregnancy, and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions.

Tapentadol vs oxycodone for postoperative pain treatment the first 7 days after total knee arthroplasty: a randomized clinical trial.

ABSTRACT: Pain after total knee arthroplasty is a prevalent condition. This study compared the effectiveness of tapentadol extended-release (ER) 50 mg × 2, oxycodone controlled-release (CR) 10 mg × 2, and placebo, as added to a multimodal analgesic regime both in-hospital and at home the first week after total knee arthroplasty. The study was randomized and blinded for investigators, staff, outcome assessors, and patients. Follow-up included pain intensity on mobilization, pain at rest, worst pain in the previous 24 hours, and adverse effects measured on 0 to 10 numerical rating scales. A total of 134 patients in 3 study groups received their allocated intervention and were included in the analysis. The primary outcome pain on mobilization the 7 first postoperative days reported as area under the curve was 528.1 (SD 267.5, interquartile range (IQR) 356.6-665.4) for placebo, 427.2 (SD 203.9, IQR 303.6-544.3) for tapentadol ER, and 507.9 (SD 243.7, IQR 292.4-686.8) for oxycodone CR (P = 0.12). With the exception of constipation being less prevalent in the tapentadol ER group (P = 0.02), we found no significant differences between treatment groups for the secondary outcomes. Tapentadol ER as an add-on to multimodal analgesia did not significantly improve pain relief when compared to oxycodone CR or placebo. Constipation was lowest in the tapentadol ER group.

Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial.

OBJECTIVE: To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years). DESIGN: Randomised controlled trial. SETTING: General population of older adults in Trondheim, Norway. PARTICIPANTS: 1567 of 6966 individuals born between 1936 and 1942. INTERVENTION: Participants were randomised to two sessions weekly of high intensity interval training at about 90% of peak heart rate (HIIT, n=400), moderate intensity continuous training at about 70% of peak heart rate (MICT, n=387), or to follow the national guidelines for physical activity (n=780; control group); all for five years. MAIN OUTCOME MEASURE: All cause mortality. An exploratory hypothesis was that HIIT lowers mortality more than MICT. RESULTS: Mean age of the 1567 participants (790 women) was 72.8 (SD 2.1) years. Overall, 87.5% of participants reported to have overall good health, with 80% reporting medium or high physical activity levels at baseline. All cause mortality did not differ between the control group and combined MICT and HIIT group. When MICT and HIIT were analysed separately, with the control group as reference (observed mortality of 4.7%), an absolute risk reduction of 1.7 percentage points was observed after HIIT (hazard ratio 0.63, 95% confidence interval 0.33 to 1.20) and an absolute increased risk of 1.2 percentage points after MICT (1.24, 0.73 to 2.10). When HIIT was compared with MICT as reference group an absolute risk reduction of 2.9 percentage points was observed (0.51, 0.25 to 1.02) for all cause mortality. Control participants chose to perform more of their physical activity as HIIT than the physical activity undertaken by participants in the MICT group. This meant that the controls achieved an exercise dose at an intensity between the MICT and HIIT groups. CONCLUSION: This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels. However, we observed a lower all cause mortality trend after HIIT compared with controls and MICT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.

Exercise training reveals micro-RNAs associated with improved cardiac function and electrophysiology in rats with heart failure after myocardial infarction.

AIMS: Endurance training improves aerobic fitness and cardiac function in individuals with heart failure. However, the underlying mechanisms are not well characterized. Exercise training could therefore act as a tool to discover novel targets for heart failure treatment. We aimed to associate changes in Ca2+ handling and electrophysiology with micro-RNA (miRNA) profile in exercise trained heart failure rats to establish which miRNAs induce heart failure-like effects in Ca2+ handling and electrophysiology. METHODS AND RESULTS: Post-myocardial infarction (MI) heart failure was induced in Sprague Dawley rats. Rats with MI were randomized to sedentary control (sed), moderate (mod)- or high-intensity (high) endurance training for 8 weeks. Exercise training improved cardiac function, Ca2+ handling and electrophysiology including reduced susceptibility to arrhythmia in an exercise intensity-dependent manner where high intensity gave a larger effect. Fifty-five miRNAs were significantly regulated (up or down) in MI-sed, of which 18 and 3 were changed towards Sham-sed in MI-high and MI-mod, respectively. Thereafter we experimentally altered expression of these "exercise-miRNAs" individually in human induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CM) in the same direction as they were changed in MI. Of the "exercise-miRNAs", miR-214-3p prolonged AP duration, whereas miR-140 and miR-208a shortened AP duration. miR-497-5p prolonged Ca2+ release whereas miR-214-3p and miR-31a-5p prolonged Ca2+ decay. CONCLUSION: Using exercise training as a tool, we discovered that miR-214-3p, miR-497-5p, miR-31a-5p contribute to heart-failure like behaviour in Ca2+ handling and electrophysiology and could be potential treatment targets.

Cardiac arrest as a reportable condition: a cohort study of the first 6 years of the Norwegian out-of-hospital cardiac arrest registry.

OBJECTIVES: The Norwegian Cardiac Arrest Registry (NorCAR) was established in 2013 when cardiac arrest became a mandatory reportable condition. The aim of this cohort study is to describe how the world's first mandatory, population-based cardiac arrest registry evolved during its first 6 years. SETTING: Norway has a total population of 5.3 million inhabitants with a population density that varies considerably. All residents are assigned a unique identifier number, giving nationally approved registries access to information about all births and deaths in the country. Data in the registry are entered by data processors; public employees with close links to the emergency medical services. All data processors undergo a standardised training and meet for yearly retraining and updates. PARTICIPANTS: All events of cardiac arrest where bystanders or healthcare professionals have started cardiopulmonary resuscitation or performed defibrillation are included into the NorCAR. PRIMARY AND SECONDARY OUTCOME MEASURES: Since the establishment of the registry, the number of reporting health trusts, the number of reported events and the corresponding population at risk were followed year by year. Outcome is measured as changes in inclusion rate, incidence per 100 000 inhabitants and survival to 30 days after cardiac arrest. RESULTS: In total, 14 849 cases were registered over 6 years, between 2013 and 2018. The number of health trusts reporting rose steadily from 2013. Within 3 years, all trusts reported to the registry with an increasing number of events reported; going from 1101 to 3400 per year. The prevalence of bystander cardiopulmonary resuscitation increased slightly, but the population incidence of survival did not change. CONCLUSION: Declaring cardiac arrest as a reportable condition and close follow-up of all reporting areas is essential when building a national registry.

Factors affecting the course of resuscitation from cardiac arrest with pulseless electrical activity in children and adolescents.

BACKGROUND: Although in-hospital pediatric cardiac arrests and cardiopulmonary resuscitation occur >15,000/year in the US, few studies have assessed which factors affect the course of resuscitation in these patients. We investigated transitions from Pulseless Electrical Activity (PEA) to Ventricular Fibrillation/pulseless Ventricular Tachycardia (VF/pVT), Return of Spontaneous Circulation (ROSC) and recurrences from ROSC to PEA in children and adolescents with in-hospital cardiac arrest. METHODS: Episodes of cardiac arrest at the Children's Hospital of Philadelphia were prospectively registered. Defibrillators that recorded chest compression depth/rate and ventilation rate were applied. CPR variables, patient characteristics and etiology, and dynamic factors (e.g. the proportion of time spent in PEA or ROSC) were entered as time-varying covariates for the transition intensities under study. RESULTS: In 67 episodes of CPR in 59 patients (median age 15 years) with cardiac arrest, there were 52 transitions from PEA to ROSC, 22 transitions from PEA to VF/pVT, and 23 recurrences of PEA from ROSC. Except for a nearly significant effect of mean compression depth beyond a threshold of 5.7 cm, only dynamic factors that evolved during CPR favored a transition from PEA to ROSC. The latter included a lower proportion of PEA over the last 5 min and a higher proportion of ROSC over the last 5 min. Factors associated with PEA to VF/pVT development were age, weight, the proportion spent in VF/pVT or PEA the last 5 min, and the general transition intensity, while PEA recurrence from ROSC only depended on the general transition intensity. CONCLUSION: The clinical course during pediatric cardiac arrest was mainly influenced by dynamic factors associated with time in PEA and ROSC. Transitions from PEA to ROSC seemed to be favored by deeper compressions.

Methadone serum concentrations and influencing factors: A naturalistic observational study.

RATIONALE: Although methadone maintenance treatment (MMT) has long been used for opioid addiction, our knowledge on its pharmacokinetics is still limited. OBJECTIVES: We aimed to investigate effects of age, gender, and various co-medications on methadone serum concentration-to-dose ratio (CDR) in a naturalistic setting. METHODS: In total, 4425 routine serum methadone concentrations obtained from 1691 MMT patients in the period October 1999 to July 2017 were included. Information about doses, age, gender, and concurrent medications was available in the laboratory database at the Department of Clinical Pharmacology at St. Olav University Hospital in Trondheim, Norway. A log-linear mixed model was used when analyzing the data. RESULTS: Mean age was 38.4 (range, 21-78) years and 70% were men. Mean CDR was 332 (range, 7-1776) (ng/mL)/(100 mg/d). Concomitant medication with at least one out of totally 170 drugs was recorded in 26% of the samples. CDRs were significantly lower in women (- 9%; confidence interval (CI), - 13%, - 4%; p = 0.001) and with concurrent use of CYP inducers (- 36%; CI, - 44%, - 28%; p < 0.001), but higher using CYP3A4 inhibitors as co-medications (+ 36%; CI, + 10%, + 68%; p = 0.005). CONCLUSIONS: Our results warrant taking into consideration gender differences in methadone metabolism as well as the impact of potential drug-drug interactions to obtain an optimal therapeutic effect and avoid adverse effects in MMT. Although the clinical implications of the altered drug levels require further study, our results call for close clinical monitoring of all patients undergoing MMT, preferably along with laboratory measurements of methadone serum concentrations.