Can perioperative pCO2 gaps predict complications in patients undergoing major elective abdominal surgery randomized to goal-directed therapy or standard care? A secondary analysis.

The difference between venous and arterial carbon dioxide pressure (pCO2 gap), has been used as a diagnostic and prognostic tool. We aimed to assess whether perioperative pCO2 gaps can predict postoperative complications. This was a secondary analysis of a multicenter RCT comparing goal-directed therapy (GDT) to standard care in which 464 patients undergoing high-risk elective abdominal surgery were included. Arterial and central venous blood samples were simultaneously obtained at four time points: after induction, at the end of surgery, at PACU/ICU admission, and PACU/ICU discharge. Complications within the first 30 days after surgery were recorded. Similar pCO2 gaps were found in patients with and without complications, except for the pCO2 gap at the end of surgery, which was higher in patients with complications (6.0 mmHg [5.0-8.0] vs. 6.0 mmHg [4.1-7.5], p = 0.005). The area under receiver operating characteristics curves for predicting complications from pCO2 gaps at all time points were between 0.5 and 0.6. A weak correlation between ScvO2 and pCO2 gaps was found for all timepoints (ρ was between - 0.40 and - 0.29 for all timepoints, p < 0.001). The pCO2 gap did not differ between GDT and standard care at any of the selected time points. In our study, pCO2 gap was a poor predictor of major postoperative complications at all selected time points. Our research does not support the use of pCO2 gap as a prognostic tool after high-risk abdominal surgery. pCO2 gaps were comparable between GDT and standard care. Clinical trial registration Netherlands Trial Registry NTR3380.

Outcome in patients undergoing postponed elective surgery during the COVID-19 pandemic (TRACE II): study protocol for a multicentre prospective observational study.

INTRODUCTION: During the COVID-19 pandemic many non-acute elective surgeries were cancelled or postponed around the world. This has created an opportunity to study the effect of delayed surgery on health conditions prior to surgery and postsurgical outcomes in patients with postponed elective surgery. The control group of the Routine Postsurgical Anesthesia Visit to Improve Patient Outcome (TRACE I) study, conducted between 2016 and 2019, will serve as a control cohort. METHODS AND ANALYSIS: TRACE II is an observational, multicentre, prospective cohort study among surgical patients with postponed surgery due to COVID-19 in academic and non-academic hospitals in the Netherlands. We aim to include 2500 adult patients. The primary outcome will be the 30-day incidence of major postoperative complications. Secondary outcome measures include the 30-day incidence of minor postoperative complications, 1 year mortality, length of stay (in hospital, medium care and intensive care), quality of recovery 30 days after surgery and postoperative quality of life up to 1 year following surgery. Multivariable logistic mixed-effects regression analysis with a random intercept for hospital will be used to test group differences on the primary outcome. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of Maastricht University Medical Centre+ and Amsterdam UMC. Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals, with a preference for open access journals. Data will be made publicly available after publication of the main results. TRIAL REGISTRATION NUMBER: NL8841.

Validation of the PreOperative Score to predict Post-Operative Mortality (POSPOM) in Dutch non-cardiac surgery patients.

BACKGROUND: Standardized risk assessment tools can be used to identify patients at higher risk for postoperative complications and death. In this study, we validate the PreOperative Score to predict Post-Operative Mortality (POSPOM) for in-hospital mortality in a large cohort of non-cardiac surgery patients. In addition, the performance of POSPOM to predict postoperative complications was studied. METHODS: Data from the control cohort of the TRACE (routine posTsuRgical Anesthesia visit to improve patient outComE) study was analysed. POSPOM scores for each patient were calculated post-hoc. Observed in-hospital mortality was compared with predicted mortality according to POSPOM. Discrimination was assessed by receiver operating characteristic curves with C-statistics for in-hospital mortality and postoperative complications. To describe the performance of POSPOM sensitivity, specificity, negative predictive values, and positive predictive values were calculated. For in-hospital mortality, calibration was assessed by a calibration plot. RESULTS: In 2490 patients, the observed in-hospital mortality was 0.5%, compared to 1.3% as predicted by POSPOM. 27.1% of patients had at least one postoperative complication of which 22.4% had a major complication. For in-hospital mortality, POSPOM showed strong discrimination with a C-statistic of 0.86 (95% CI, 0.78-0.93). For the prediction of complications, the discrimination was poor to fair depending on the severity of the complication. The calibration plot showed poor calibration of POSPOM with an overestimation of in-hospital mortality. CONCLUSION: Despite the strong discriminatory performance, POSPOM showed poor calibration with an overestimation of in-hospital mortality. Performance of POSPOM for the prediction of any postoperative complication was poor but improved according to severity.

Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study.

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. DISCUSSION: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. TRIAL REGISTRATION: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

Vital Signs Prediction for COVID-19 Patients in ICU.

This study introduces machine learning predictive models to predict the future values of the monitored vital signs of COVID-19 ICU patients. The main vital sign predictors include heart rate, respiration rate, and oxygen saturation. We investigated the performances of the developed predictive models by considering different approaches. The first predictive model was developed by considering the following vital signs: heart rate, blood pressure (systolic, diastolic and mean arterial, pulse pressure), respiration rate, and oxygen saturation. Similar to the first approach, the second model was developed using the same vital signs, but it was trained and tested based on a leave-one-subject-out approach. The third predictive model was developed by considering three vital signs: heart rate (HR), respiration rate (RR), and oxygen saturation (SpO2). The fourth model was a leave-one-subject-out model for the three vital signs. Finally, the fifth predictive model was developed based on the same three vital signs, but with a five-minute observation rate, in contrast with the aforementioned four models, where the observation rate was hourly to bi-hourly. For the five models, the predicted measurements were those of the three upcoming observations (on average, three hours ahead). Based on the obtained results, we observed that by limiting the number of vital sign predictors (i.e., three vital signs), the prediction performance was still acceptable, with the average mean absolute percentage error (MAPE) being 12%,5%, and 21.4% for heart rate, oxygen saturation, and respiration rate, respectively. Moreover, increasing the observation rate could enhance the prediction performance to be, on average, 8%,4.8%, and 17.8% for heart rate, oxygen saturation, and respiration rate, respectively. It is envisioned that such models could be integrated with monitoring systems that could, using a limited number of vital signs, predict the health conditions of COVID-19 ICU patients in real-time.

Perioperative goal-directed therapy in high-risk abdominal surgery. A multicenter randomized controlled superiority trial.

STUDY OBJECTIVE: The potential of perioperative goal-directed therapy (PGDT) to improve outcome after high-risk abdominal surgery remains subject of debate. In particular, there is a need for large, multicenter trials focusing on relevant patient outcomes to confirm the evidence found in small, single center studies including minor complications in their composite endpoints. The present study therefore aims to investigate the effect of an arterial waveform analysis based PGDT algorithm on the incidence of major complications including mortality after high-risk abdominal surgery. DESIGN: Prospective randomized controlled multicenter trial. SETTING: Operating theatres and Post-Anesthesia/Intensive Care units (PACU/ICU) of four tertiary hospitals in The Netherlands. PATIENTS: A total number of 482 patients undergoing elective, abdominal surgery that is considered high-risk due to the extent of the procedure and/or patient comorbidities. INTERVENTIONS: Hemodynamic therapy using an age-specific PGDT algorithm including cardiac index (CI) and stroke volume variation (SVV) measurements during a 24-h perioperative period starting at induction of anesthesia. MEASUREMENTS: The average number of major complications (including mortality) within 30 days after surgery, the number of minor complications, hospital and PACU/ICU length of stay (LOS), amounts of fluids and vasoactive medications used. Complications were graded using the Accordion severity grading system. RESULTS: The average number of major complications per patient was 0.79 (PGDT group) versus 0.69 (control group) (p = 0.195). There were no statistically significant differences in the number of minor complications, hospital LOS, PACU/ICU LOS, or grading of complications. Patients in the PGDT group received more fluids intraoperatively, more dobutamine intra- and postoperatively, while patients in the control group received more phenylephrine during the operation. CONCLUSIONS: PGDT based on a CI and SVV driven algorithm did not result in improved outcomes after high-risk abdominal surgery. CLINICAL TRIAL REGISTRATION: Netherlands Trial Registry: NTR3380.

Impact of Procedural Sedation on the Clinical Outcome of Microelectrode Recording Guided Deep Brain Stimulation in Patients with Parkinson's Disease.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) has become a routine treatment of advanced Parkinson's disease (PD). DBS surgery is commonly performed under local anesthesia (LA) to obtain reliable microelectrode recordings. However, procedural sedation and/or analgesia (PSA) is often desirable to improve patient comfort. The impact of PSA in addition to LA on outcome is largely unknown. Therefore, we performed an observational study to assess the effect of PSA compared to LA alone during STN DBS surgery on outcome in PD patients. METHODS: Seventy PD patients (22 under LA, 48 under LA + PSA) scheduled for STN DBS implantation were included. Dexmedetomidine, clonidine or remifentanil were used for PSA. The primary outcome was the change in Movement Disorders Society Unified Parkinson's Disease Rating Score III (MDS-UPDRS III) and levodopa equivalent daily dosage (LEDD) between baseline, one month before surgery, and twelve months postoperatively. Secondary outcome measures were motor function during activities of daily living (MDS-UPDRS II), cognitive alterations and surgical adverse events. Postoperative assessment was conducted in "on" stimulation and "on" medication conditions. RESULTS: At twelve months follow-up, UPDRS III and UPDRS II scores in "on" medication conditions were similar between the LA and PSA groups. The two groups showed a similar LEDD reduction and an equivalent decline in executive function measured by the Stroop Color-Word Test, Trail Making Test-B, and verbal fluency. The incidence of perioperative and postoperative adverse events was similar between groups. CONCLUSION: This study demonstrates that PSA during STN DBS implantation surgery in PD patients was not associated with differences in motor and non-motor outcome after twelve months compared with LA only.

Vital Signs Prediction and Early Warning Score Calculation Based on Continuous Monitoring of Hospitalised Patients Using Wearable Technology.

In this prospective, interventional, international study, we investigate continuous monitoring of hospitalised patients' vital signs using wearable technology as a basis for real-time early warning scores (EWS) estimation and vital signs time-series prediction. The collected continuous monitored vital signs are heart rate, blood pressure, respiration rate, and oxygen saturation of a heterogeneous patient population hospitalised in cardiology, postsurgical, and dialysis wards. Two aspects are elaborated in this study. The first is the high-rate (every minute) estimation of the statistical values (e.g., minimum and mean) of the vital signs components of the EWS for one-minute segments in contrast with the conventional routine of 2 to 3 times per day. The second aspect explores the use of a hybrid machine learning algorithm of kNN-LS-SVM for predicting future values of monitored vital signs. It is demonstrated that a real-time implementation of EWS in clinical practice is possible. Furthermore, we showed a promising prediction performance of vital signs compared to the most recent state of the art of a boosted approach of LSTM. The reported mean absolute percentage errors of predicting one-hour averaged heart rate are 4.1, 4.5, and 5% for the upcoming one, two, and three hours respectively for cardiology patients. The obtained results in this study show the potential of using wearable technology to continuously monitor the vital signs of hospitalised patients as the real-time estimation of EWS in addition to a reliable prediction of the future values of these vital signs is presented. Ultimately, both approaches of high-rate EWS computation and vital signs time-series prediction is promising to provide efficient cost-utility, ease of mobility and portability, streaming analytics, and early warning for vital signs deterioration.

TRACE (Routine posTsuRgical Anesthesia visit to improve patient outComE): a prospective, multicenter, stepped-wedge, cluster-randomized interventional study.

BACKGROUND: Perioperative complications occur in 30-40% of non-cardiac surgical patients and are the leading cause of early postoperative morbidity and mortality. Regular visits by trained health professionals may decrease the incidence of complications and mortality through earlier detection and adequate treatment of complications. Until now, no studies have been performed on the impact of routine postsurgical anesthesia visits on the incidence of postoperative complications and mortality. METHODS: TRACE is a prospective, multicenter, stepped-wedge cluster randomized interventional study in academic and peripheral hospitals in the Netherlands. All hospitals start simultaneously with a control phase in which standard care is provided. Sequentially, in a randomized order, hospitals cross over to the intervention phase in which patients at risk are routinely followed up by an anesthesia professional at postoperative days 1 and 3, aiming to detect and prevent or treat postoperative complications. We aim to include 5600 adult patients who are at high risk of developing complications. The primary outcome variable is 30-day postoperative mortality. Secondary outcomes include incidence of postoperative complications and postoperative quality of life up to one year following surgery. Statistical analyses will be performed to compare the control and intervention cohorts with multilevel linear and logistic regression models, adjusted for temporal trends and for clusters (hospitals). The time horizon of the economic (cost-effectiveness) evaluation will be 30 days and one year following surgery. DISCUSSION: TRACE is the first to study the effects of a routine postoperative visit by an anesthesia healthcare professional on mortality and cost-effectiveness of surgical patients. If the intervention proves to be beneficial for the patient and cost-effective, the stepped-wedge design ensures direct implementation in the participating hospitals. TRIAL REGISTRATION: Nederlands Trial Register/Netherlands Trial Registration, NTR5506 . Registered on 02 December 2015.

Medicine Goes Female: Protocol for Improving Career Options of Females and Working Conditions for Researching Physicians in Clinical Medical Research by Organizational Transformation and Participatory Design.

BACKGROUND: All European countries need to increase the number of health professionals in the near future. Most efforts have not brought the expected results so far. The current notion is that this is mainly related to the fact that female physicians will clearly outnumber their male colleagues within a few years in nearly all European countries. Still, women are underrepresented in leadership and research positions throughout Europe. OBJECTIVES: The MedGoFem project addresses multiple perspectives with the participation of multiple stakeholders. The goal is to facilitate the implementation of Gender Equality Plans (GEP) in university hospitals; thereby, transforming the working conditions for women working as researchers and highly qualified physicians simultaneously. Our proposed innovation, a crosscutting topic in all research and clinical activities, must become an essential part of university hospital strategic concepts. METHODS: We capture the current status with gender-sensitive demographic data concerning medical staff and conduct Web-based surveys to identify cultural, country-specific, and interdisciplinary factors conducive to women's academic success. Individual expectations of employees regarding job satisfaction and working conditions will be visualized based on "personal construct theory" through repertory grids. An expert board working out scenarios and a gender topic agenda will identify culture-, nation-, and discipline-specific aspects of gender equality. University hospitals in 7 countries will establish consensus groups, which work on related topics. Hospital management supports the consensus groups, valuates group results, and shares discussion results and suggested measures across groups. Central findings of the consensus groups will be prepared as exemplary case studies for academic teaching on research and work organization, leadership, and management. RESULTS: A discussion group on gender equality in academic medicine will be established on an internationally renowned open-research platform. Project results will be published in peer-reviewed journals with high-impact factors. In addition, workshops on gender dimension in research using the principles of Gendered Innovation will be held. Support and consulting services for hospitals will be introduced in order to develop a European consulting service. CONCLUSIONS: The main impact of the project will be the implementation of innovative GEP tailored to the needs of university hospitals, which will lead to measurable institutional change in gender equality. This will impact the research at university hospitals in general, and will improve career prospects of female researchers in particular. Simultaneously, the gender dimension in medical research as an innovation factor and mandatory topic will be strengthened and integrated in each individual university hospital research activity. Research funding organizations can use the built knowledge to include mandatory topics for funding applications to enforce the use and implementation of GEP in university hospitals.

LucKi Birth Cohort Study: rationale and design.

BACKGROUND: Infancy and childhood are characterized by rapid growth and development, which largely determine health status and well-being across the lifespan. Identification of modifiable risk factors and prognostic factors in critical periods of life will contribute to the development of effective prevention and intervention strategies. The LucKi Birth Cohort Study was designed and started in 2006 to follow children from birth into adulthood on a wide range of determinants, disorders, and diseases. During preschool and school years, the primary focus is on the etiology and prognosis of atopic diseases (eczema, asthma, and hay fever) and overweight/obesity. METHODS/DESIGN: LucKi is an ongoing, dynamic, prospective birth cohort study, embedded in the Child and Youth Health Care (CYHC) practice of the 'Westelijke Mijnstreek' (a region in the southeast of the Netherlands). Recruitment (1-2 weeks after birth) and follow-up (until 19 years) coincide with routine CYHC contact moments, during which the child's physical and psychosocial development is closely monitored, and anthropometrics are measured repeatedly in a standardised way. Information gathered through CYHC is complemented with repeated parental questionnaires, and information from existing registries of pharmacy, hospital and/or general practice. Since the start already more than 5,000 children were included in LucKi shortly after birth, reaching an average participation rate of ~65 %. DISCUSSION: The LucKi Birth Cohort Study provides a framework in which children are followed from birth into adulthood. Embedding LucKi in CYHC simplifies implementation, leads to low maintenance costs and high participation rates, and facilitates direct implementation of study results into CYHC practice. Furthermore, LucKi provides opportunities to initiate new (experimental) studies and/or to establish biobanking in (part of) the cohort, and contributes relevant information on determinants and health outcomes to policy and decision makers. Cohort details can be found on www.birthcohorts.net .

Trends in wheeze in Dutch school children and the role of medication use.

BACKGROUND: While the prevalence of childhood wheeze continues to increase in many countries, decreasing trends have also been reported. This may be explained by increased use of asthma medication, which effectively suppresses wheeze symptoms. In this study we investigated trends in wheeze in Dutch school children between 1989 and 2005, and their association with medication use. METHODS: In five repeated cross-sectional surveys between 1989 and 2005, parents of all 5- to 6-year-old and 8- to 11-year-old children eligible for a routine physical examination were asked to complete a questionnaire on their child's respiratory health. We identified all children for whom a questionnaire was completed in two successive surveys. Children were grouped according to birth year and classified into one out of four wheeze categories: "no wheeze," "discontinued wheeze," "continued wheeze," or "new-onset wheeze." RESULTS: In total, 3,339 children, born in 1983 (N = 670), 1988 (N = 607), 1992 (N = 980), and 1995 (N = 1,082), participated twice. Over the study period, the proportion of children with "no wheeze" increased from 73.8% to 86.1% (Ptrend < 0.001), while the proportion of children with "discontinued" and "continued" wheeze decreased from 13.2% to 6.3% (Ptrend < 0.001) and from 8.8% to 3.1% (Ptrend < 0.001), respectively. Medication use was consistently associated only with the presence of wheeze symptoms and this association did not change over time (Pbirth year × medication use > 0.05 for all wheeze categories). CONCLUSION: An increasing trend of Dutch school children with "no wheeze," and decreasing trends of children with "discontinued" and "continued" wheeze between 1989 and 2005 could not be explained by (increased) medication use. This suggests that wheeze prevalence is not masked by medication use, but is truly declining.

Early life growth and the development of preschool wheeze, independent from overweight: the LucKi Birth Cohort Study.

OBJECTIVE: To investigate whether birth weight and postnatal growth rates are independently related to the development of overweight and wheeze up to age 3 years. STUDY DESIGN: Children from the LucKi Birth Cohort Study with complete follow-up for repeated questionnaires (at age 0, 7, and 14 months and 3 years) and informed consent to use height and weight data (measured by trained personnel at age 0, 7, and 14 months and 2 and 3 years) were included (n = 566). Wheeze (parental-reported) and overweight (body mass index [BMI] >85th percentile) were regressed with generalized estimating equations on birth weight and relative growth rates (difference SDS for weight, height, and BMI). RESULTS: Higher birth weight and higher weight and BMI growth rates were associated with increased risk of overweight, but not of wheeze, up to age 3 years. Higher height growth rate was associated with lower risk of wheeze up to 3 years, independent of overweight (aOR, 0.65; 95% CI, 0.53-0.79). In time-lag models, wheeze was associated with subsequently reduced height growth up to age 14 months, but not vice versa. CONCLUSION: Only height growth rate, and not weight and BMI growth rate, is associated with preschool wheeze, independent of overweight. Children who wheeze demonstrate a subsequent reduction in height growth up to age 14 months, but not vice versa. Because height growth rate is not associated with overweight, preschool wheeze and overweight are not associated throughout early life growth.

Effect of smoke-free legislation on the incidence of sudden circulatory arrest in the Netherlands.

OBJECTIVE: To investigate whether smoke-free legislation in the Netherlands led to a decreased incidence of out-of-hospital sudden circulatory arrest (SCA). Smoke-free legislation was implemented in two phases: a workplace ban in 2004 and an extension of this ban to the hospitality sector on 1 July 2008. DESIGN: Weekly incidence data on SCA were obtained from the ambulance registry of South Limburg, the Netherlands. Three time periods were distinguished: the pre-ban period (1 January 2002-1 January 2004), the first post-ban period (1 January 2004-1 July 2008) and the second post-ban period (1 July 2008-1 May 2010). Trends in absolute SCA incidence were analysed using Poisson regression, adjusted for population size, ambient temperature, air pollution and influenza rates. RESULTS: A total of 2305 SCA cases were observed (mean weekly incidence 5.3±2.3 SD). The adjusted Poisson regression model showed a small but significant increase in SCA incidence during the pre-ban period (+0.20% cases per week, p=0.044). This trend changed significantly after implementation of the first ban (with -0.24% cases per week, p=0.043), translating into a 6.8% (22 cases) reduction in the number of SCA cases after 1 year of smoke-free legislation. No further decrease was seen after the second smoking ban. CONCLUSIONS: After introduction of a nationwide workplace smoking ban in 2004, a significant decrease in the incidence of out-of-hospital SCA was seen in South Limburg. Poor enforcement of the 2008 hospitality sector ban may account for the fact that no further decrease in the incidence of SCA was seen at this time.

Trends in socioeconomic inequalities in smoking prevalence, consumption, initiation, and cessation between 2001 and 2008 in the Netherlands. Findings from a national population survey.

BACKGROUND: Widening of socioeconomic status (SES) inequalities in smoking prevalence has occurred in several Western countries from the mid 1970's onwards. However, little is known about a widening of SES inequalities in smoking consumption, initiation and cessation. METHODS: Repeated cross-sectional population surveys from 2001 to 2008 (n ≈ 18,000 per year) were used to examine changes in smoking prevalence, smoking consumption (number of cigarettes per day), initiation ratios (ratio of ever smokers to all respondents), and quit ratios (ratio of former smokers to ever smokers) in the Netherlands. Education level and income level were used as indicators of SES and results were reported separately for men and women. RESULTS: Lower educated respondents were significantly more likely to be smokers, smoked more cigarettes per day, had higher initiation ratios, and had lower quit ratios than higher educated respondents. Income inequalities were smaller than educational inequalities and were not all significant, but were in the same direction as educational inequalities. Among women, educational inequalities widened significantly between 2001 and 2008 for smoking prevalence, smoking initiation, and smoking cessation. Among low educated women, smoking prevalence remained stable between 2001 and 2008 because both the initiation and quit ratio increased significantly. Among moderate and high educated women, smoking prevalence decreased significantly because initiation ratios remained constant, while quit ratios increased significantly. Among men, educational inequalities widened significantly between 2001 and 2008 for smoking consumption only. CONCLUSIONS: While inequalities in smoking prevalence were stable among Dutch men, they increased among women, due to widening inequalities in both smoking cessation and initiation. Both components should be addressed in equity-oriented tobacco control policies.