Marginal structural models with monotonicity constraints: A case study in out-of-hospital cardiac arrest patients.

This paper deals with estimating the probability of a binary counterfactual outcome as a function of a continuous covariate under monotonicity constraints. We are motivated by the study of out-of-hospital cardiac arrest patients which aims to estimate the counterfactual 30-day survival probability if either all patients had received, or if none of the patients had received bystander cardiopulmonary resuscitation (CPR), as a function of the ambulance response time. It is natural to assume that the counterfactual 30-day survival probability cannot increase with increasing ambulance response time. We model the monotone relationship with a marginal structural model and B-splines. We then derive an estimating equation for the parameters of interest which however further relies on an auxiliary regression model for the observed 30-day survival probabilities. The predictions of the observed 30-day survival probabilities are used as pseudo-values for the unobserved counterfactual 30-day survival status. The methods are illustrated and contrasted with an unconstrained modeling approach in large-scale Danish registry data.

Food purchases in households with and without diabetes based on consumer purchase data.

OBJECTIVES: Dietary recommendations for individuals with diabetes are easy to provide, but adherence is difficult to monitor. The objective of this study was to investigate whether there was a difference in grocery purchases between households with and without diabetes. STUDY DESIGN: Cohort study. METHODS: Consumer purchase data in 2019 was collected from 6662 households donating their supermarket receipts via a receipt collecting service. Of these households, 718 included at least one individual with diabetes. The monetary percentages spent on specific food groups were used to characterize households using all purchases in 2019. A probability index model was used to compare households with diabetes to households without diabetes. RESULTS: We included 405,264 shopping trips in 2019 attributed to 6662 households. Both households with and without diabetes spent the highest monetary percentage on sweets (with diabetes: 9.3%, without diabetes: 8.8%), with no statistically significant difference detected. However, compared to households without diabetes, households with diabetes had a significantly higher probability of spending a higher monetary percentage on butter, oil and dressings; non-sugary drinks; processed red meat and ready meals as well as a significantly lower probability of spending a higher monetary percentage on accessory compounds; alcoholic beverages; eggs; grains; rice and pasta, and raw vegetables. CONCLUSIONS: Households with diabetes spent a relatively higher monetary value on several unhealthy foods and less on several healthy groceries compared to households without diabetes. There is a need for more diabetes self-management education focused on including more healthy dietary choices in their household grocery purchases.

Temporal changes in risk of cardiovascular events in people with newly diagnosed type 2 diabetes with and without cardiovascular disease.

AIMS: Examine temporal changes in the risk of cardiovascular events in people with newly diagnosed type 2 diabetes with and without cardiovascular disease (CVD). METHODS: 283,600 individuals with newly diagnosed type 2 diabetes and age-, sex-, and CVD-matched controls without diabetes were identified through Danish nationwide registries between 1997 and 2014. Using Cox regression models, we report the standardized absolute 5-year risk of cardiovascular death, myocardial infarction, stroke, and heart failure for people with diabetes and controls. RESULTS: Individuals with newly diagnosed diabetes were at increased risk of cardiovascular events compared to controls. From 1997-2002 to 2009-2014 reductions in cardiovascular events for people with diabetes were: cardiovascular death; 26.5% to 13.8% in people with CVD and from 7.3% to 3.2% in people without CVD, myocardial infarction; 13.1% to 6.5% in people with CVD and from 4.1% to 1.9% in people without CVD, stroke; 14.2% to 8.8% in people with CVD and from 4.9% to 2.2% in people without CVD, and heart failure; 21.0% to 13.8% in people with CVD and from 5.0% to 2.6% in people without CVD. The risk of cardiovascular events declined more among people with diabetes than controls. CONCLUSIONS: Newly diagnosed type 2 diabetes was associated with an increased risk of cardiovascular events, and the risk decreased significantly 1997-2014 in both people with and without CVD. Furthermore, the excess risk associated with type 2 diabetes decreased significantly during the study period.

Cardiovascular outcomes with GLP-1 receptor agonists vs. SGLT-2 inhibitors in patients with type 2 diabetes.

AIMS: We examined cardiovascular outcomes associated with initiation of glucagon-like peptide-1 receptor agonist (GLP-1RA) vs. sodium-glucose co-transporter-2 inhibitor (SGLT-2i) treatment in a real-world setting among patients with type 2 diabetes. METHODS AND RESULTS: This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first-ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8913 new users of GLP-1RA and 5275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was as follows: composite cardiovascular outcome, 5.6% [95% confidence interval (CI): 5.2-6.1] vs. 5.6% (95% CI: 4.8-6.3); cardiovascular mortality, 1.6% (95% CI: 1.3-1.9) vs. 1.5% (95% CI: 1.1-1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5-2.0) vs. 1.8% (95% CI: 1.2-2.5); myocardial infarction, 2.1% (95% CI: 1.8-2.4) vs. 2.1% (95% CI: 1.5-2.6); and stroke, 2.5% (95% CI: 2.2-2.9) vs. 2.6% (95% CI: 2.2-3.1). CONCLUSION: In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA vs. SGLT-2i was not found to be associated with significant differences in cardiovascular risk.

Enteral nutrition and dynamics of citrulline and intestinal fatty acid-binding protein in adult ICU patients.

BACKGROUND AND AIMS: Plasma citrulline and intestinal fatty acid binding protein (I-FABP) are biomarkers reflecting enterocyte function and intestinal mucosal injury. The aim was to describe daily dynamics of citrulline and I-FABP concentrations in association with enteral nutrition (EN) in adult ICU patients. We hypothesized that success or failure of EN is reflected by differences in citrulline and I-FABP levels at admission, as well as in daily dynamics over the first week. METHODS: The present study was a planned sub-study of the iSOFA study (ClinicalTrials.gov Identifier: NCT02613000). With delayed informed consent we included adult (18 years or older) patients admitted for unlimited care to 5 ICUs in Europe. Citrulline and I-FABP were assessed and nutritional data recorded daily during the first week of the patients' ICU stay. RESULTS: The study included 224 patients with 693 plasma samples analyzed for citrulline and 695 for I-FABP. The median ICU stay was 2 (IQR 1-4) days and 35 patients (15.6 %) stayed in the ICU for ≥ 7 days. The majority of patients (184/224; 82.1 %) received EN or oral nutrition (ON) during their ICU stay, in 164 patients (73.2 %) nutrition was started within 48 h of admission (early enteral or oral nutrition, EEN/ON). Median biomarker concentrations on admission were: citrulline 24.5 (IQR 18.1-31.7) µmol/L and I-FABP 2763 (1326-4805) pg/mL. Reference range for citrulline was 17-46 µmol/L and for I-FABP 377-2049 pg/mL. Patients with EEN/ON demonstrated an increase in citrulline concentrations over the first week in ICU unlike those not receiving EEN/ON (P = 0.049 for the mean log-citrulline values over time between groups) as well as higher average citrulline concentrations. Success of EEN/ON (80 % of caloric target achieved by day 4) was associated with citrulline values increasing from day 4, whereas a slight decrease was observed with unsuccessful EEN/ON. However, these dynamics over time were not statistically significantly different (P = 0.654). Patients with EEN/ON unexpectedly had I-FABP values higher than those without (average values for all days P = 0.004). Median I-FABP values on day 3 were higher with successful EEN/ON (646 (IQR 313-1116) vs 278 (IQR 190-701) pg/mL, P = 0.022). CONCLUSIONS: EEN/ON was associated with higher values and different dynamics of citrulline over the first week in ICU. No clear difference of measured biomarkers was seen when patients were compared according to success of EEN/ON. Our study does not allow suggesting certain thresholds of citrulline nor I-FABP that could be used for bedside decision-making with regard to EN. This study was a planned sub-study of the iSOFA study (ClinicalTrials.gov Identifier: NCT02613000).

Estimation of causal effect in integrating randomized clinical trial and observational data - An example application to cardiovascular outcome trial.

Safety evaluation of drug development is a comprehensive process across the product lifecycle. While a randomized clinical trial (RCT) can provide high-quality data to assess the efficacy and safety of a new intervention, the pre-marketing trials are limited in statistical power to detect causal elevation of rare but potentially serious adverse events. On the other hand, real-world data (RWD) sources play a critical role in further understanding the safety profile of the new intervention. Bringing together the breadth and strength of RWD and RCT data, we can maximize the utility of RWD and answer broader questions. In this manuscript, we propose a three-step statistical framework to corroborate findings from both RCT and RWD for evaluating important safety concerns identified in the pre-marketing setting. By the proposed approach, we first match the observational study to RCT, then the causal estimation is validated via the matched observational study with the target RCT by targeted maximum likelihood estimation (TMLE) method, and lastly the evidence from RCT and RWD can be combined in an integrative analysis. A potential application to cardiovascular outcome trials for type 2 diabetes mellitus is illustrated. Finally, simulation results suggest that the heterogeneity of patient population from RCT and RWD can lead to varying degrees of treatment effect estimation and the proposed approach may be able to mitigate such difference in the integrative analysis.

Socioeconomic disparities in prehospital factors and survival after out-of-hospital cardiac arrest.

OBJECTIVE: It remains unknown whether patient socioeconomic factors affect interventions and survival after out-of-hospital cardiac arrest (OHCA), and whether a socioeconomic effect on bystander interventions affects survival. Therefore, this study examined patient socioeconomic disparities in prehospital factors and survival. METHODS: From the Danish Cardiac Arrest Registry, patients with OHCA ≥30 years were identified, 2001-2014, and divided into quartiles of household income (highest, high, low, lowest). Associations between income and bystander cardiopulmonary resuscitation (CPR) and 30-day survival with bystander CPR as mediator were analysed by logistic regression and mediation analysis in private witnessed, public witnessed, private unwitnessed and public unwitnessed arrests, adjusted for confounders. RESULTS: We included 21 480 patients. Highest income patients were younger, had higher education and were less comorbid relative to lowest income patients. They had higher odds for bystander CPR with the biggest difference in private unwitnessed arrests (OR 1.74, 95% CI 1.47 to 2.05). For 30-day survival, the biggest differences were in public witnessed arrests with 26.0% (95% CI 22.4% to 29.7%) higher survival in highest income compared with lowest income patients. Had bystander CPR been the same for lowest income as for highest income patients, then survival would be 25.3% (95% CI 21.5% to 29.0%) higher in highest income compared with lowest income patients, resulting in elimination of 0.79% (95% CI 0.08% to 1.50%) of the income disparity in survival. Similar trends but smaller were observed in low and high-income patients, the other three subgroups and with education instead of income. From 2002 to 2014, increases were observed in both CPR and survival in all income groups. CONCLUSION: Overall, lower socioeconomic status was associated with poorer prehospital factors and survival after OHCA that was not explained by patient or cardiac arrest-related factors.

The Mediating Effect of Pupils' Physical Fitness on the Relationship Between Family Socioeconomic Status and Academic Achievement in a Danish School Cohort.

INTRODUCTION: Family socioeconomic status influences pupils' academic achievements, and studies have established positive associations between physical fitness and academic achievements. However, whether physical fitness mediates the relationship remains unknown. OBJECTIVE: We investigated if pupils' physical fitness mediates the pathway between family socioeconomic status and academic achievement using causal inference-based mediation analysis. METHODS: This study included 527 girls and 552 boys between 13 and 15 years of age from the Danish municipality of Aalborg. Physical fitness was measured through VO2max tests in 2010 and demographic data were obtained from nationwide registers. Family socioeconomic status was classified into four levels ranging from 1 to 4, where level 1 represents the lowest and level 4 the highest based on either family income or education. RESULTS: Controlling for sex, ethnicity, age, and parents' cohabitation status, all total effects display higher academic achievement with increased family socioeconomic status. Splitting the effects, the direct effects reveal the existence of other pathways not involving physical fitness. The indirect effects established physical fitness as a mediator showing that pupils from family socioeconomic status levels one, three, and four changes grade by - 0.13 [95% confidence interval (CI) - 0.26, - 0.01], 0.07 (95% CI 0.00, 0.14), and 0.24 (95% CI 0.14, 0.34), respectively, compared to socioeconomic status level two. The corresponding proportions mediated are 18% (95% CI 1, 57), 6% (95 CI 0, 13), and 12% (95% CI 7, 18) when family socioeconomic status is based on education. Classifying family socioeconomic status on income, pupils from family socioeconomic status levels one, three, and four show grade changes of - 0.07 (95% CI - 0.16, 0.02), 0.22 (95% CI 0.13, 0.32), and 0.26 (95% CI 0.15, 0.37), respectively, compared to socioeconomic status level two. The corresponding proportions mediated are 12% (95% CI - 6, 41), 30% (95% CI 16, 54), and 20% (95% CI 12, 32). CONCLUSION: In conclusion, pupils' physical fitness partially mediated the pathway between family socioeconomic status and academic achievement.

Incidence, Risk Factors, and Outcomes of Intra-Abdominal Hypertension in Critically Ill Patients-A Prospective Multicenter Study (IROI Study).

OBJECTIVES: To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population. DESIGN: Prospective observational study. SETTING: Fifteen ICUs worldwide. PATIENTS: Consecutive adult ICU patients with a bladder catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28- and 90-day mortality, whereas the presence of intra-abdominal hypertension on the day of ICU admission did not predict mortality. Body mass index, Acute Physiology and Chronic Health Evaluation II score greater than or equal to 18, presence of abdominal distension, absence of bowel sounds, and positive end-expiratory pressure greater than or equal to 7 cm H2O were independently associated with the development of intra-abdominal hypertension at any time during the observation period. In subjects without intra-abdominal hypertension on day 1, body mass index combined with daily positive fluid balance and positive end-expiratory pressure greater than or equal to 7 cm H2O (as documented on the day before intra-abdominal hypertension occurred) were associated with the development of intra-abdominal hypertension during the first week in the ICU. CONCLUSIONS: In our mixed ICU patient cohort, intra-abdominal hypertension occurred in almost half of all subjects and was twice as prevalent in mechanically ventilated patients as in spontaneously breathing patients. Presence and severity of intra-abdominal hypertension during the observation period significantly and independently increased 28- and 90-day mortality. Five admission day variables were independently associated with the presence or development of intra-abdominal hypertension. Positive fluid balance was associated with the development of intra-abdominal hypertension after day 1.

Workplace bullying and workplace violence as risk factors for cardiovascular disease: a multi-cohort study.

AIMS: To assess the associations between bullying and violence at work and cardiovascular disease (CVD). METHODS AND RESULTS: Participants were 79 201 working men and women, aged 18-65 years and free of CVD and were sourced from three cohort studies from Sweden and Denmark. Exposure to workplace bullying and violence was measured at baseline using self-reports. Participants were linked to nationwide health and death registers to ascertain incident CVD, including coronary heart disease and cerebrovascular disease. Study-specific results were estimated by marginal structural Cox regression and were combined using fixed-effect meta-analysis. Nine percent reported being bullied at work and 13% recorded exposure to workplace violence during the past year. We recorded 3229 incident CVD cases with a mean follow-up of 12.4 years (765 in the first 4 years). After adjustment for age, sex, country of birth, marital status, and educational level, being bullied at work vs. not was associated with a hazard ratio (HR) of 1.59 [95% confidence interval (CI) 1.28-1.98] for CVD. Experiencing workplace violence vs. not was associated with a HR of 1.25 (95% CI 1.12-1.40) for CVD. The population attributable risk was 5.0% for workplace bullying and 3.1% for workplace violence. The excess risk remained similar in analyses with different follow-up lengths, cardiovascular risk stratifications, and after additional adjustments. Dose-response relations were observed for both workplace bullying and violence (Ptrend < 0.001). There was only negligible heterogeneity in study-specific estimates. CONCLUSION: Bullying and violence are common at workplaces and those exposed to these stressors are at higher risk of CVD.

The effect of early-life and adult socioeconomic position on development of lifestyle-related diseases.

BACKGROUND: Early-life socioeconomic position (SEP) is associated with lifestyle-related diseases in adulthood. However, evidence is lacking on the extent to which adult SEP mediates this association. METHODS: Time to either chronic obstructive pulmonary disease (COPD), cardiovascular disease or diabetes were assessed in the Danish population born between 1961 and 1971 (n = 793 674) from age 30 until 2015. Early-life position was assessed in 1981 (by parental) and again at age 30 (own) by four markers; income, occupation, education-divided into high, middle, low-and a combined score for all markers. Using a counterfactual approach, we estimated the total effect of early-life position on disease onset and the degree to which adult position mediated this effect. RESULTS: Results of the time-to-event analysis showed a gradient of all early-life markers on the risk of developing all lifestyle-related diseases. Notably, comparing those in the lowest to the highest educational position, the hazard of COPD was 130% higher for women [hazard ratio = 2.30(95% confidence interval = 2.20-2.41)] and 114% higher for men [2.14 (2.05-2.25)]. About 67%(63-70%) of the effect of educational position was mediated through adult position for COPD, 55% for cardiovascular disease and 50% for diabetes. For the combined score 44, 29 and 33%, respectively, was mediated. CONCLUSION: About one-tenth to two-thirds of the effect of early-life position is mediated by the position attained in adulthood. The degree mediated depend on the outcome investigated, gender and the social position marker used indicating that alternative pathways may play a key role in developing effective policies targeting early-life behaviours.

Workplace bullying and violence as risk factors for type 2 diabetes: a multicohort study and meta-analysis.

AIMS/HYPOTHESIS: The aim of this multicohort study was to examine whether employees exposed to social stressors at work, such as workplace bullying and violence, have an increased risk of type 2 diabetes. METHODS: The study included 45,905 men and women (40-65 years of age and free of diabetes at baseline) from four studies in Sweden, Denmark and Finland. Workplace bullying and violence were self-reported at baseline. Incident diabetes was ascertained through national health and medication records and death registers. Marginal structural Cox models adjusted for age, sex, country of birth, marital status and educational level were used for the analyses. RESULTS: Nine per cent of the population reported being bullied at work and 12% were exposed to workplace violence or threats of violence. Bullied participants had a 1.46 (95% CI 1.23, 1.74) times higher risk of developing diabetes compared with non-bullied participants. Exposure to violence or threats of violence was also associated with a higher risk of diabetes (HR 1.26 [95% CI 1.02, 1.56]). The risk estimates attenuated slightly when taking BMI into account, especially for bullying. The results were similar for men and women, and were consistent across cohorts. CONCLUSIONS/INTERPRETATION: We found a higher risk of incident type 2 diabetes among employees exposed to bullying or violence in the workplace. Further research is needed to determine whether policies to reduce bullying and violence at work may reduce the incidence of type 2 diabetes in working populations. Research on the mechanisms is also highly warranted.

The indirect and direct pathways between physical fitness and academic achievement on commencement in post-compulsory education in a historical cohort of Danish school youth.

BACKGROUND: Some studies have found positive associations between physical fitness and academic achievements. Pupils' academic achievements should indicate scholastic abilities to commence a post-compulsory education. However, the effect magnitude of physical fitness and academic achievements on commencement in post-compulsory education is unknown. We examined the pathways between physical fitness and academic achievement on pupils' commencement in post-compulsory education. METHODS: This historical cohort study followed 530 girls and 554 boys from the Danish municipality of Aalborg in the period 2008-2014, 13 to 15 years old in 2010. Physical fitness was assessed through a watt-max cycle ergometer test represented as VO2max (mL·kg-1·min-1). Academic achievement, commencement status and information on covariates were obtained from Danish nationwide registers. Causal inference based mediation analysis was used to investigate the indirect and direct pathways by separating the total effect of physical fitness on post-compulsory education commencement. RESULTS: Adjusting for sex, age, ethnicity and socioeconomic status, the overall mediation analysis showed an odds ratio (OR) of 1.87 (95% confidence interval (CI): 1.30; 2.73) for the total effect, corresponding to an increase in odds of post-compulsory education commencement when the physical fitness was increased by 10 units of VO2max. The separated total effect showed a natural direct OR of 1.36 (95% CI: 0.93; 1.98) and a natural indirect (i.e., through academic achievement) OR of 1.37 (95% CI: 1.20; 1.57). Thus, 51% (95% CI: 27%; 122%) of the effect of physical fitness on post-compulsory education commencement was mediated through academic achievement. CONCLUSION: Physical fitness had a positive effect on post-compulsory education commencement. A substantial part of this effect was mediated through academic achievement.

Risk factors of coercion among psychiatric inpatients: a nationwide register-based cohort study.

PURPOSE: Reducing the use of coercion among patients with mental disorders has long been a political priority. However, risk factors for coercive measures have primarily been investigated in smaller studies. To reduce the use of coercion, it is crucial to identify people at risk which we aim to do in this first large-scale study. METHODS: A cohort study was conducted among all psychiatric inpatients in Denmark, following 112,233 individuals during 1999-2014. Data from Danish registers were analysed using logistic regression for repeated measures. RESULTS: 24,594 inpatients were exposed to a coercive measure (21.9%). Clinical characteristics were the foremost predictors of coercion and patients with organic mental disorder had the highest increased risk of being subjected to a coercive measure (OR = 5.56; 95% CI = 5.04, 6.14). The risk of coercion was the highest in the first admission and decreased with the number of admissions (all p < 0.001). The following socioeconomic variables were associated with an increased risk of coercion: male sex, unemployment, lower social class and immigrants from low and middle income countries (all p < 0.001). Early retirement and social relations, such as being married and having children, reduced the risk of being subjected to coercive measure (all p < 0.05). CONCLUSION: From our nationwide data, we identified a broad range of risk factors associated with coercive measures. Our findings can assist researchers in identifying patients at risk of coercion and thereby help targeting new coercion reduction programs.

Implementation of enteral feeding protocol in an intensive care unit: Before-and-after study.

AIM: To determine the effects of implementing an enteral feeding protocol on the nutritional delivery and outcomes of intensive care patients. METHODS: An uncontrolled, observational before-and-after study was performed in a tertiary mixed medical-surgical intensive care unit (ICU). In 2013, a nurse-driven enteral feeding protocol was developed and implemented in the ICU. Nutrition and outcome-related data from patients who were treated in the study unit from 2011-2012 (the Before group) and 2014-2015 (the After group) were obtained from a local electronic database, the national Population Registry and the hospital's Infection Control Service. Data from adult patients, readmissions excluded, who were treated for at least 7 d in the study unit were analysed. RESULTS: In total, 231 patients were enrolled in the Before and 249 in the After group. The groups were comparable regarding demographics, patient profile, and severity of illness. Fewer patients were mechanically ventilated on admission in the After group (86.7% vs 93.1% in the Before group, P = 0.021). The prevalence of hospital-acquired infections, length of ICU stay and ICU, 30- and 60-d mortality did not differ between the groups. Patients in the After group had a lower 90-d (P = 0.026) and 120-d (P = 0.033) mortality. In the After group, enteral nutrition was prescribed less frequently (P = 0.039) on day 1 but significantly more frequently on all days from day 3. Implementation of the feeding protocol resulted in a higher cumulative amount of enterally (P = 0.049) and a lower cumulative amount of parenterally (P < 0.001) provided calories by day 7, with an overall reduction in caloric provision (P < 0.001). The prevalence of gastrointestinal symptoms was comparable in both groups, as was the frequency of prokinetic use. Underfeeding (total calories < 80% of caloric needs, independent of route) was observed in 59.4% of the study days Before vs 76.9% After (P < 0.001). Inclusion in the Before group, previous abdominal surgery, intra-abdominal hypertension and the sum of gastrointestinal symptoms were found to be independent predictors of insufficient enteral nutrition. CONCLUSION: The use of a nurse-driven feeding protocol improves the delivery of enteral nutrition in ICU patients without concomitant increases in gastrointestinal symptoms or intra-abdominal hypertension.

Simulation-based multiprofessional obstetric anaesthesia training conducted in situ versus off-site leads to similar individual and team outcomes: a randomised educational trial.

OBJECTIVE: To investigate the effect of in situ simulation (ISS) versus off-site simulation (OSS) on knowledge, patient safety attitude, stress, motivation, perceptions of simulation, team performance and organisational impact. DESIGN: Investigator-initiated single-centre randomised superiority educational trial. SETTING: Obstetrics and anaesthesiology departments, Rigshospitalet, University of Copenhagen, Denmark. PARTICIPANTS: 100 participants in teams of 10, comprising midwives, specialised midwives, auxiliary nurses, nurse anaesthetists, operating theatre nurses, and consultant doctors and trainees in obstetrics and anaesthesiology. INTERVENTIONS: Two multiprofessional simulations (clinical management of an emergency caesarean section and a postpartum haemorrhage scenario) were conducted in teams of 10 in the ISS versus the OSS setting. PRIMARY OUTCOME: Knowledge assessed by a multiple choice question test. EXPLORATORY OUTCOMES: Individual outcomes: scores on the Safety Attitudes Questionnaire, stress measurements (State-Trait Anxiety Inventory, cognitive appraisal and salivary cortisol), Intrinsic Motivation Inventory and perceptions of simulations. Team outcome: video assessment of team performance. Organisational impact: suggestions for organisational changes. RESULTS: The trial was conducted from April to June 2013. No differences between the two groups were found for the multiple choice question test, patient safety attitude, stress measurements, motivation or the evaluation of the simulations. The participants in the ISS group scored the authenticity of the simulation significantly higher than did the participants in the OSS group. Expert video assessment of team performance showed no differences between the ISS versus the OSS group. The ISS group provided more ideas and suggestions for changes at the organisational level. CONCLUSIONS: In this randomised trial, no significant differences were found regarding knowledge, patient safety attitude, motivation or stress measurements when comparing ISS versus OSS. Although participant perception of the authenticity of ISS versus OSS differed significantly, there were no differences in other outcomes between the groups except that the ISS group generated more suggestions for organisational changes. TRIAL REGISTRATION NUMBER: NCT01792674.

Comparison of different definitions of feeding intolerance: A retrospective observational study.

BACKGROUND & AIMS: While feeding intolerance (FI) is clinically important in the critically ill it is inconsistently defined. By evaluating definitions of FI based on relationships between symptoms and signs of gastrointestinal (GI) dysfunction and mortality the objective was to define FI using the definition that was most strongly associated with subsequent mortality. METHODS: Data from all adult patients admitted to a single ICU between 2004 and 2011, and who were receiving enteral nutrition (EN), were analysed. The amount of EN administered, presence of absent bowel sounds (BS), vomiting and/or regurgitation, diarrhoea, bowel distension, and large gastric residual volumes (GRVs) were documented daily. A GRV ≥500 ml/day was considered as large and the sum of gastrointestinal (GI) symptoms including large GRV was calculated daily. Various definitions of FI were modelled. Definitions using only GRV, or GRV with other GI symptoms, or GRV and failure to reach preset EN targets were evaluated. The predictive power of FI on mortality was tested by adding the presence of FI (different definitions were tested one-by-one) into multiple regression analyses together with admission day demographic and severity of illness variables. RESULTS: Of the 1712 patients included, 221 (12.9%) died in ICU and 495 (28.9%) had died within 90 days after ICU admission. The definition of FI based on the presence of at least three out of five GI symptoms was most strongly related to ICU-mortality (6.3% prevalence in survivors vs. 23.5% in non-survivors, p < 0.001, odds ratio (95%CI) 3.39 (2.23-5.14)), whereas EN <23% of caloric target was the strongest predictor for mortality 90 days after admission (50.7% prevalence among survivors vs 75.2% in non-survivors, p < 0.001, odds ratio (95% CI) 2.34 (1.80-3.04)). CONCLUSIONS: FI is associated with increased mortality but the strength of this relationship depends on the definition used. The 'best' definition of FI for prediction of ICU-mortality is based on a complex assessment of GI symptoms (including large GRV), whereas enteral underfeeding is the definition of FI that is the strongest predictor of death within 90 days of admission. Our 'best' definitions are not immediately generalizable, but should help building up future studies.

Postoperative complications and mortality after major gastrointestinal surgery.

BACKGROUND AND OBJECTIVE: The incidence of postoperative complications and death is low in the general population, but a subgroup of high-risk patients can be identified amongst whom adverse postoperative outcomes occur more frequently. The present study was undertaken to describe the incidence of postoperative complications, length of stay, and mortality after major abdominal surgery for gastrointestinal, hepatobiliary and pancreatic malignancies and to identify the risk factors for impaired outcome. MATERIAL AND METHODS: Data of patients, operated on for gastro-intestinal malignancies during 2009-2010 were retrieved from the clinical database of Tartu University Hospital. Major outcome data included incidence of postoperative complications, hospital-, 30-day, 90-day and 1-year mortality, and length of ICU and hospital stay. High-risk patients were defined as patients with American Society of Anesthesiologists (ASA) physical status ≥3 and revised cardiac risk index (RCRI) ≥3. Multivariate analysis was used to determine the risk factors for postoperative mortality and morbidity. RESULTS: A total of 507 (259 men and 248 women, mean age 68.3±11.3 years) were operated on for gastrointestinal, hepatobiliary, or pancreatic malignancies during 2009 and 2010 in Tartu University Hospital, Department of Surgical Oncology. 25% of the patients were classified as high risk patients. The lengths of intensive care and hospital stay were 4.4±7 and 14.5±10 days, respectively. The rate of postoperative complications was 33.5% in the total cohort, and 44% in high-risk patients. The most common complication was delirium, which occurred in 12.8% of patients. For patients without high risk (ASA130min, and positive fluid balance >1300mL after the 1st postoperative day, were identified as independent risk factors for the development of complications. CONCLUSION: The complication rate after major gastro-intestinal surgery is high. ASA physical status and revised cardiac risk index adequately reflect increased risk for postoperative complications and worse short and long-term outcome.