One-year transplant-free survival following hospital discharge after ICU admission for ACLF in the Netherlands.

BACKGROUND & AIMS: Patients with acute decompensation of cirrhosis or acute-on-chronic liver failure (ACLF) often require intensive care unit (ICU) admission for organ support. Existing research, mostly from specialized liver transplant centers, largely addresses short-term outcomes. Our aim was to evaluate in-hospital mortality and 1-year transplant-free survival after hospital discharge in the Netherlands. METHODS: We conducted a nationwide observational cohort study, including patients with a history of cirrhosis or first complications of cirrhotic portal hypertension admitted to ICUs in the Netherlands between 2012 and 2020. The influence of ACLF grade at ICU admission on 1-year transplant-free survival after hospital discharge among hospital survivors was evaluated using unadjusted Kaplan-Meier survival curves and an adjusted Cox proportional hazard model. RESULTS: Out of the 3,035 patients, 1,819 (59.9%) had ACLF-3. 1,420 patients (46.8%) survived hospitalization after ICU admission. The overall probability of 1-year transplant-free survival after hospital discharge was 0.61 (95% CI 0.59-0.64). This rate varied with ACLF grade at ICU admission, being highest in patients without ACLF (0.71; 95% CI 0.66-0.76) and lowest in those with ACLF-3 (0.53 [95% CI 0.49-0.58]) (log-rank p <0.0001). However, after adjusting for age, malignancy status and MELD score, ACLF grade at ICU admission was not associated with an increased risk of liver transplantation or death within 1 year after hospital discharge. CONCLUSION: In this nationwide cohort study, ACLF grade at ICU admission did not independently affect 1-year transplant-free survival after hospital discharge. Instead, age, presence of malignancy and the severity of liver disease played a more prominent role in influencing transplant-free survival after hospital discharge. IMPACT AND IMPLICATIONS: Patients with acute-on-chronic liver failure often require intensive care unit (ICU) admission for organ support. In these patients, short-term mortality is high, but long-term outcomes of survivors remain unknown. Using a large nationwide cohort of ICU patients, we discovered that the severity of acute-on-chronic liver failure at ICU admission does not influence 1-year transplant-free survival after hospital discharge. Instead, age, malignancy status and overall severity of liver disease are more critical factors in determining their long-term survival.

Strain on Scarce Intensive Care Beds Drives Reduced Patient Volumes, Patient Selection, and Worse Outcome: A National Cohort Study.

OBJECTIVES: Strain on ICUs during the COVID-19 pandemic required stringent triage at the ICU to distribute resources appropriately. This could have resulted in reduced patient volumes, patient selection, and worse outcome of non-COVID-19 patients, especially during the pandemic peaks when the strain on ICUs was extreme. We analyzed this potential impact on the non-COVID-19 patients. DESIGN: A national cohort study. SETTING: Data of 71 Dutch ICUs. PARTICIPANTS: A total of 120,393 patients in the pandemic non-COVID-19 cohort (from March 1, 2020 to February 28, 2022) and 164,737 patients in the prepandemic cohort (from January 1, 2018 to December 31, 2019). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Volume, patient characteristics, and mortality were compared between the pandemic non-COVID-19 cohort and the prepandemic cohort, focusing on the pandemic period and its peaks, with attention to strata of specific admission types, diagnoses, and severity. The number of admitted non-COVID-19 patients during the pandemic period and its peaks were, respectively, 26.9% and 34.2% lower compared with the prepandemic cohort. The pandemic non-COVID-19 cohort consisted of fewer medical patients (48.1% vs. 50.7%), fewer patients with comorbidities (36.5% vs. 40.6%), and more patients on mechanical ventilation (45.3% vs. 42.4%) and vasoactive medication (44.7% vs. 38.4%) compared with the prepandemic cohort. Case-mix adjusted mortality during the pandemic period and its peaks was higher compared with the prepandemic period, odds ratios were, respectively, 1.08 (95% CI, 1.05-1.11) and 1.10 (95% CI, 1.07-1.13). CONCLUSIONS: In non-COVID-19 patients the strain on healthcare has driven lower patient volume, selection of fewer comorbid patients who required more intensive support, and a modest increase in the case-mix adjusted mortality.

Predicting 30-day mortality in intensive care unit patients with ischaemic stroke or intracerebral haemorrhage.

BACKGROUND: Stroke patients admitted to an intensive care unit (ICU) follow a particular survival pattern with a high short-term mortality, but if they survive the first 30 days, a relatively favourable subsequent survival is observed. OBJECTIVES: The development and validation of two prognostic models predicting 30-day mortality for ICU patients with ischaemic stroke and for ICU patients with intracerebral haemorrhage (ICH), analysed separately, based on parameters readily available within 24 h after ICU admission, and with comparison with the existing Acute Physiology and Chronic Health Evaluation IV (APACHE-IV) model. DESIGN: Observational cohort study. SETTING: All 85 ICUs participating in the Dutch National Intensive Care Evaluation database. PATIENTS: All adult patients with ischaemic stroke or ICH admitted to these ICUs between 2010 and 2019. MAIN OUTCOME MEASURES: Models were developed using logistic regressions and compared with the existing APACHE-IV model. Predictive performance was assessed using ROC curves, calibration plots and Brier scores. RESULTS: We enrolled 14 303 patients with stroke admitted to ICU: 8422 with ischaemic stroke and 5881 with ICH. Thirty-day mortality was 27% in patients with ischaemic stroke and 41% in patients with ICH. Important factors predicting 30-day mortality in both ischaemic stroke and ICH were age, lowest Glasgow Coma Scale (GCS) score in the first 24 h, acute physiological disturbance (measured using the Acute Physiology Score) and the application of mechanical ventilation. Both prognostic models showed high discrimination with an AUC 0.85 [95% confidence interval (CI), 0.84 to 0.87] for patients with ischaemic stroke and 0.85 (0.83 to 0.86) in ICH. Calibration plots and Brier scores indicated an overall good fit and good predictive performance. The APACHE-IV model predicting 30-day mortality showed similar performance with an AUC of 0.86 (95% CI, 0.85 to 0.87) in ischaemic stroke and 0.87 (0.86 to 0.89) in ICH. CONCLUSION: We developed and validated two prognostic models for patients with ischaemic stroke and ICH separately with a high discrimination and good calibration to predict 30-day mortality within 24 h after ICU admission. TRIAL REGISTRATION: Trial registration: Dutch Trial Registry ( https://www.trialregister.nl/ ); identifier: NTR7438.

Age Moderates the Effect of Obesity on Mortality Risk in Critically Ill Patients With COVID-19: A Nationwide Observational Cohort Study.

OBJECTIVES: A high body mass index (BMI) is associated with an unfavorable disease course in COVID-19, but not among those who require admission to the ICU. This has not been examined across different age groups. We examined whether age modifies the association between BMI and mortality among critically ill COVID-19 patients. DESIGN: An observational cohort study. SETTING: A nationwide registry analysis of critically ill patients with COVID-19 registered in the National Intensive Care Evaluation registry. PATIENTS: We included 15,701 critically ill patients with COVID-19 (10,768 males [68.6%] with median [interquartile range] age 64 yr [55-71 yr]), of whom 1,402 (8.9%) patients were less than 45 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the total sample and after adjustment for age, gender, Acute Physiology and Chronic Health Evaluation IV, mechanical ventilation, and use of vasoactive drugs, we found that a BMI greater than or equal to 30 kg/m 2 does not affect hospital mortality (adjusted odds ratio [OR adj ] = 0.98; 95% CI, 0.90-1.06; p = 0.62). For patients less than 45 years old, but not for those greater than or equal to 45 years old, a BMI greater than or equal to 30 kg/m 2 was associated with a lower hospital mortality (OR adj = 0.59; 95% CI, 0.36-0.96; p = 0.03). CONCLUSIONS: A higher BMI may be favorably associated with a lower mortality among those less than 45 years old. This is in line with the so-called "obesity paradox" that was established for other groups of critically ill patients in broad age ranges. Further research is needed to understand this favorable association in young critically ill patients with COVID-19.

Risk of psychosis among migrants to the Netherlands by time since arrival.

BACKGROUND: The high risk of psychosis among migrants is often attributed to social stressors in the host country. We examined whether the relative risk of psychosis among migrants is low on arrival and increases thereafter. METHODS: In this cohort study, first-generation immigrants to the Netherlands, aged 10 years and older (N = 1 281 678), were matched by birth year and sex to 2 542 313 native-born Dutch controls. The first occurrence of psychosis after arrival was established using data on dispensing of antipsychotic medication (APM) (during 2006-2017) and on insurance claims for treatment of psychosis (2011-2016). The Incidence Rate Ratios (IRRs) for migrants compared to controls were estimated by year since arrival. RESULTS: The IRR of APM was 0.22 (95% CI 0.21-0.24) in the year of arrival ('year 1') and increased gradually to 1.39 (1.19-1.62) after 10 or more years. The IRR of an insurance claim increased from 0.57 (0.51-0.62) to 1.87 (1.38-2.55) in year 5. Among migrants from sub-Saharan Africa, the IRR of an insurance claim was already high in year 1 [2.46 (1.95-3.11)], especially when aged 10-20 years at arrival [6.09 (2.93-12.64)]. Among migrants from other non-Western countries, the IRR was already significantly increased in year 2 [1.28 (1.03-1.59)]. CONCLUSIONS: The relative risk of psychosis among migrants was generally low at arrival and increased thereafter. The increased IRRs in the early years after arrival among those from non-Western countries indicate that for these groups certain risk factors are already relevant shortly after arrival.

The risk of psychosis for transgender individuals: a Dutch national cohort study.

BACKGROUND: The stressful minority position of transgender persons may result in a high risk of psychosis. Conflicting data suggest that the observed risk depends on setting of recruitment. We assessed the relative risk of non-affective psychotic disorder (NAPD) in a large, representative cohort of transgender persons. METHODS: This cohort was composed using: data on legal sex change from the Dutch population registry and data on dispensing of cross-sex hormones (route 1), and a registry of insurance claims from mental health care including persons with a diagnosis of gender identity disorder (DSM-IV) or gender dysphoria (DSM-5) (route 2). They were matched by sex at birth, calendar year and country of birth to controls from the general population. Transgender persons (N = 5564) and controls (N = 27 820), aged 16-60 years at 1 January 2011, were followed until the first insurance claim for NAPD in 2011-2019. RESULTS: The incidence rate ratio (IRR) of NAPD for transgender persons selected exclusively through route 1 (N = 3859, IRR = 2.00, 95%-CI 1.52-2.63) was increased, but significantly lower than the IRRs for those selected exclusively through route 2 (N = 694, IRR = 22.15, 95%-CI 13.91-35.28) and for those found by both routes (N = 1011, IRR = 5.17, 95%-CI 3.57-7.49; p value for differences in IRR < 0.001). CONCLUSIONS: This study supports the social defeat-hypothesis of NAPD. The results also show the presence of a substantial number of transgender persons with severe psychiatric problems who have not (yet) taken steps to gender-affirmative care.

Trends in Early and Late Mortality in Patients With Severe Acute Pancreatitis Admitted to ICUs: A Nationwide Cohort Study.

OBJECTIVES: To investigate national mortality trends over a 12-year period for patients with severe acute pancreatitis (SAP) admitted to Dutch ICUs. Additionally, an assessment of outcome in SAP was undertaken to differentiate between early (< 14 d of ICU admission) and late (> 14 d of ICU admission) mortality. DESIGN: Data from the Dutch National Intensive Care Evaluation and health insurance companies' databases were extracted. Outcomes included 14-day, ICU, hospital, and 1-year mortality. Mortality before and after 2010 was compared using mixed logistic regression and mixed Cox proportional-hazards models. Sensitivity analyses, excluding early mortality, were performed to assess trends in late mortality. SETTING: Not applicable. PATIENTS: Consecutive adult patients with SAP admitted to all 81 Dutch ICUs between 2007 and 2018. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Among 4,160 patients treated in 81 ICUs, 14-day mortality was 17%, ICU mortality 17%, hospital mortality 23%, and 1-year mortality 33%. After 2010 in-hospital mortality adjusted for age, sex, modified Marshall, and Acute Physiology and Chronic Health Evaluation III scores were lower (odds ratio [OR], 0.76; 95% CI, 0.61-0.94) than before 2010. There was no change in ICU and 1-year mortality. Sensitivity analyses excluding patients with early mortality demonstrated a decreased ICU mortality (OR, 0.45; 95% CI, 0.32-0.64), decreased in-hospital (OR, 0.48; 95% CI, 0.36-0.63), and decreased 1-year mortality (hazard ratio, 0.81; 95% CI, 0.68-0.96) after 2010 compared with 2007-2010. CONCLUSIONS: Over the 12-year period examined, mortality in patients with SAP admitted to Dutch ICUs did not change, although after 2010 late mortality decreased. Novel therapies should focus on preventing early mortality in SAP.

The incidence of psychotic disorders among migrants and minority ethnic groups in Europe: findings from the multinational EU-GEI study.

BACKGROUND: In Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: 'minorities'). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population). METHODS: The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of Diseases, 10th edition, codes F20-F33) from 13 sites. RESULTS: The standardized incidence rates for minorities, combined into one category, varied from 12.2 in Valencia to 82.5 per 100 000 in Paris. These rates were generally high at sites with high rates for the reference population, and low at sites with low rates for the reference population. IRRs for minorities (combined into one category) varied from 0.70 (95% CI 0.32-1.53) in Valencia to 2.47 (95% CI 1.66-3.69) in Paris (test for interaction: p = 0.031). At most sites, IRRs were higher for persons from non-Western countries than for those from Western countries, with the highest IRRs for individuals from sub-Saharan Africa (adjusted IRR = 3.23, 95% CI 2.66-3.93). CONCLUSIONS: Incidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.

The effect of treatment and clinical course during Emergency Department stay on severity scoring and predicted mortality risk in Intensive Care patients.

BACKGROUND: Treatment and the clinical course during Emergency Department (ED) stay before Intensive Care Unit (ICU) admission may affect predicted mortality risk calculated by the Acute Physiology and Chronic Health Evaluation (APACHE)-IV, causing lead-time bias. As a result, comparing standardized mortality ratios (SMRs) among hospitals may be difficult if they differ in the location where initial stabilization takes place. The aim of this study was to assess to what extent predicted mortality risk would be affected if the APACHE-IV score was recalculated with the initial physiological variables from the ED. Secondly, to evaluate whether ED Length of Stay (LOS) was associated with a change (delta) in these APACHE-IV scores. METHODS: An observational multicenter cohort study including ICU patients admitted from the ED. Data from two Dutch quality registries were linked: the Netherlands Emergency department Evaluation Database (NEED) and the National Intensive Care Evaluation (NICE) registry. The ICU APACHE-IV, predicted mortality, and SMR based on data of the first 24 h of ICU admission were compared with an ED APACHE-IV model, using the most deviating physiological variables from the ED or ICU. RESULTS: A total of 1398 patients were included. The predicted mortality from the ICU APACHE-IV (median 0.10; IQR 0.03-0.30) was significantly lower compared to the ED APACHE-IV model (median 0.13; 0.04-0.36; p < 0.01). The SMR changed from 0.63 (95%CI 0.54-0.72) to 0.55 (95%CI 0.47-0.63) based on ED APACHE-IV. Predicted mortality risk changed more than 5% in 321 (23.2%) patients by using the ED APACHE-IV. ED LOS > 3.9 h was associated with a slight increase in delta APACHE-IV of 1.6 (95% CI 0.4-2.8) compared to ED LOS < 1.7 h. CONCLUSION: Predicted mortality risks and SMRs calculated by the APACHE IV scores are not directly comparable in patients admitted from the ED if hospitals differ in their policy to stabilize patients in the ED before ICU admission. Future research should focus on developing models to adjust for these differences.

One-year Mortality of Cancer Patients with an Unplanned ICU Admission: A Cohort Analysis Between 2008 and 2017 in the Netherlands.

Introduction: A decrease in short-term mortality of critically ill cancer patients with an unplanned intensive care unit (ICU) admission has been described. Few studies describe a change over time of 1-year mortality. Therefore, we examined the 1-year mortality of cancer patients (hematological or solid) with an unplanned ICU admission and we described whether the mortality changed over time. Methods: We used the National Intensive Care Evaluation (NICE) registry and extracted all patients with an unplanned ICU admission in the Netherlands between 2008 and 2017. The primary outcome was 1-year mortality, analyzed with a mixed-effects Cox proportional hazard regression. We compared the 1-year mortality of cancer patients to that of patients without cancer. Furthermore, we examined changes in mortality over the study period. Results: We included 470,305 patients: 10,401 with hematological cancer, 35,920 with solid cancer, and 423,984 without cancer. The 1-year mortality rates were 60.1%, 46.2%, and 28.3% respectively (P< .01). Approximately 30% of the cancer patients surviving their hospital admission died within 1 year, this was 12% in patients without cancer. In hematological patients, 1-year mortality decreased between 2008 and 2011, after which it stabilized. In solid cancer patients, inspection showed neither an increasing nor decreasing trend over the inclusion period. For patients without cancer, 1-year mortality decreased between 2008 and 2013, after which it stabilized. A clear decrease in hospital mortality was seen within all three groups. Conclusion: The 1-year mortality of cancer patients with an unplanned ICU admission (hematological and solid) was higher than that of patients without cancer. About one-third of the cancer patients surviving their hospital admission died within 1 year after ICU admission. We found a decrease in 1-year mortality until 2011 in hematology patients and no decrease in solid cancer patients. Our results suggest that for many cancer patients, an unplanned ICU admission is still a way to recover from critical illness, and it does not necessarily lead to success in long-term survival. The underlying type of malignancy is an important factor for long-term outcomes in patients recovering from critical illness.

Comparison of patient characteristics and long-term mortality between transferred and non-transferred COVID-19 patients in Dutch intensive care units: A national cohort study.

BACKGROUND: COVID-19 patients were often transferred to other intensive care units (ICUs) to prevent that ICUs would reach their maximum capacity. However, transferring ICU patients is not free of risk. We aim to compare the characteristics and outcomes of transferred versus non-transferred COVID-19 ICU patients in the Netherlands. METHODS: We included adult COVID-19 patients admitted to Dutch ICUs between March 1, 2020 and July 1, 2021. We compared the patient characteristics and outcomes of non-transferred and transferred patients and used a Directed Acyclic Graph to identify potential confounders in the relationship between transfer and mortality. We used these confounders in a Cox regression model with left truncation at the day of transfer to analyze the effect of transfers on mortality during the 180 days after ICU admission. RESULTS: We included 10,209 patients: 7395 non-transferred and 2814 (27.6%) transferred patients. In both groups, the median age was 64 years. Transferred patients were mostly ventilated at ICU admission (83.7% vs. 56.2%) and included a larger proportion of low-risk patients (70.3% vs. 66.5% with mortality risk <30%). After adjusting for age, APACHE IV mortality probability, BMI, mechanical ventilation, and vasoactive medication use, the hazard of mortality during the first 180 days was similar for transferred patients compared to non-transferred patients (HR [95% CI] = 0.99 [0.91-1.08]). CONCLUSIONS: Transferred COVID-19 patients are more often mechanically ventilated and are less severely ill compared to non-transferred patients. Furthermore, transferring critically ill COVID-19 patients in the Netherlands is not associated with mortality during the first 180 days after ICU admission.

Association Between an Increase in Serum Sodium and In-Hospital Mortality in Critically Ill Patients.

OBJECTIVES: In critically ill patients, dysnatremia is common, and in these patients, in-hospital mortality is higher. It remains unknown whether changes of serum sodium after ICU admission affect mortality, especially whether normalization of mild hyponatremia improves survival. DESIGN: Retrospective cohort study. SETTING: Ten Dutch ICUs between January 2011 and April 2017. PATIENTS: Adult patients were included if at least one serum sodium measurement within 24 hours of ICU admission and at least one serum sodium measurement 24-48 hours after ICU admission were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A logistic regression model adjusted for age, sex, and Acute Physiology and Chronic Health Evaluation-IV-predicted mortality was used to assess the difference between mean of sodium measurements 24-48 hours after ICU admission and first serum sodium measurement at ICU admission (Δ48 hr-[Na]) and in-hospital mortality. In total, 36,660 patients were included for analysis. An increase in serum sodium was independently associated with a higher risk of in-hospital mortality in patients admitted with normonatremia (Δ48 hr-[Na] 5-10 mmol/L odds ratio: 1.61 [1.44-1.79], Δ48 hr-[Na] > 10 mmol/L odds ratio: 4.10 [3.20-5.24]) and hypernatremia (Δ48 hr-[Na] 5-10 mmol/L odds ratio: 1.47 [1.02-2.14], Δ48 hr-[Na] > 10 mmol/L odds ratio: 8.46 [3.31-21.64]). In patients admitted with mild hyponatremia and Δ48 hr-[Na] greater than 5 mmol/L, no significant difference in hospital mortality was found (odds ratio, 1.11 [0.99-1.25]). CONCLUSIONS: An increase in serum sodium in the first 48 hours of ICU admission was associated with higher in-hospital mortality in patients admitted with normonatremia and in patients admitted with hypernatremia.

Migration and dementia: a meta-analysis of epidemiological studies in Europe.

BACKGROUND: To provide an overview of epidemiological studies of dementia among migrant groups in Europe and to estimate their pooled odds ratio (OR) v. the reference population. METHODS: Search for articles reporting on incidence or prevalence of dementia among ethnic minorities and migrants in Europe, published before 21 December 2018. We performed several meta-analyses, using a random-effects model, and, when there was no evidence of heterogeneity, a fixed-effects model. We distinguished between all migrants, African-Europeans and Asian-Europeans. RESULTS: We retrieved five population-based surveys and two health care record studies. The latter included one incidence study, the remainder were prevalence studies. The meta-analysis of all studies yielded a pooled OR, adjusted for age and sex, of 1.73 (95% CI 1.42-2.11) for dementia in all migrant groups. However, the pooled OR of population surveys (3.10; 95% CI 2.12-4.51) was significantly higher than that for the health care record studies (OR 0.94; 95% CI 0.80-1.11). The pooled ORs for African-Europeans and Asian-Europeans, based on population surveys, were 2.54 (95% CI 1.70-3.80) and 5.36 (95% CI 2.78-10.31), respectively. CONCLUSIONS: The discrepancy between health care record studies and population surveys suggests that many migrants remain undiagnosed. Migrants from Asia and Africa seem to be at significantly increased risk of dementia in Europe. Since the prevalence rates in their countries of origin are generally not higher than those for natives in Europe, there may be a parallel with the epidemiology of schizophrenia.

Clozapine and mortality: A comparison with other antipsychotics in a nationwide Danish cohort study.

OBJECTIVE: To compare the mortality in people using clozapine to that of people using other antipsychotics. METHODS: Danish incidence cohort of 22,110 patients with a first diagnosis of non-affective psychotic disorder (1995-2013) and a prevalence cohort of 50,881 patients ever diagnosed with such a disorder (1969-2013). Hazard ratios (HR) were calculated for the antipsychotic drug used at the time of death ("current use": incidence and prevalence cohort) and for the drug used for the longest at that moment ("cumulative use": incidence cohort), using a Cox model with adjustment for somatic comorbidity. Clozapine was the reference drug. RESULTS: As for current drug use, the risk of suicide was higher among users of other antipsychotics in the incidence (HRadj  = 1.76; 95% CI 0.72-4.32) and prevalence (HRadj  = 2.20; 95% CI 1.35-3.59) cohorts. There was no significant difference in all-cause or cardiovascular mortality in the two cohorts. Cumulative use of clozapine was not associated with an increased cardiovascular mortality. Cumulative use of other antipsychotics for up to 1 year was associated with a lower all-cause mortality and suicide risk than a similar period of clozapine use (all-cause: HRadj  = 0.73; 95% CI 0.63-0.85, suicide; HRadj  = 0.65; 95% CI 0.46-0.91). CONCLUSION: The results indicate that the use of clozapine is not associated with increased cardiovascular mortality. We found opposing trends toward a lower risk of suicide during current use of clozapine and a higher risk of suicide associated with cumulative use up to 1 year. This suggests that clozapine cessation marks a period of high risk of suicide.

Long-Term Mortality Among ICU Patients With Stroke Compared With Other Critically Ill Patients.

OBJECTIVES: Assessment of all-cause mortality of intracerebral hemorrhage and ischemic stroke patients admitted to the ICU and comparison to the mortality of other critically ill ICU patients classified into six other diagnostic subgroups and the general Dutch population. DESIGN: Observational cohort study. SETTING: All ICUs participating in the Dutch National Intensive Care Evaluation database. PATIENTS: All adult patients admitted to these ICUs between 2010 and 2015; patients were followed until February 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of all 370,386 included ICU patients, 7,046 (1.9%) were stroke patients, 4,072 with ischemic stroke, and 2,974 with intracerebral hemorrhage. Short-term mortality in ICU-admitted stroke patients was high with 30 days mortality of 31% in ischemic stroke and 42% in intracerebral hemorrhage. In the longer term, the survival curve gradient among ischemic stroke and intracerebral hemorrhage patients stabilized. The gradual alteration of mortality risk after ICU admission was assessed using left-truncation with increasing minimum survival period. ICU-admitted stroke patients who survive the first 30 days after suffering from a stroke had a favorable subsequent survival compared with other diseases necessitating ICU admission such as patients admitted due to sepsis or severe community-acquired pneumonia. After having survived the first 3 months after ICU admission, multivariable Cox regression analyses showed that case-mix adjusted hazard ratios during the follow-up period of up to 3 years were lower in ischemic stroke compared with sepsis (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.36) and severe community-acquired pneumonia (adjusted hazard ratio, 1.57; 95% CI, 1.39-1.77) and in intracerebral hemorrhage patients compared with these groups (adjusted hazard ratio, 1.14; 95% CI, 0.98-1.33 and adjusted hazard ratio, 1.49; 95% CI, 1.28-1.73). CONCLUSIONS: Stroke patients who need intensive care treatment have a high short-term mortality risk, but this alters favorably with increasing duration of survival time after ICU admission in patients with both ischemic stroke and intracerebral hemorrhage, especially compared with other populations of critically ill patients such as sepsis or severe community-acquired pneumonia patients.

Migration and psychosis: a meta-analysis of incidence studies.

BACKGROUND: The aims of this meta-analysis are (i) to estimate the pooled relative risk (RR) of developing non-affective psychotic disorder (NAPD) and affective psychotic disorder (APD) among migrants and their children; (ii) to adjust these results for socioeconomic status (SES); (iii) to examine the sources of heterogeneity that underlie the risk of NAPD. METHODS: We included population-based incidence studies that reported an age-adjusted RR with 95% confidence interval (CI) published 1 January 1977-12 October 2017 and used a random-effects model. RESULTS: We retrieved studies performed in Europe (n = 43), Israel (n = 3), Canada (n = 2) and Australia (n = 1). The meta-analysis yielded a RR, adjusted for age and sex, of 2.13 (95% CI 1.99-2.27) for NAPD and 2.94 (95% CI 2.28-3.79) for APD. The RRs diminished, but persisted after adjustment for SES. With reference to NAPD: a personal or parental history of migration to Europe from countries outside Europe was associated with a higher RR (RR = 2.94, 95% CI 2.63-3.29) than migration within Europe (RR = 1.88, 95% 1.62-2.18). The corresponding RR was lower in Israel (RR = 1.22; 0.99-1.50) and Canada (RR = 1.21; 0.85-1.74). The RR was highest among individuals with a black skin colour (RR = 4.19, 95% CI 3.42-5.14). The evidence of a difference in risk between first and second generation was insufficient. CONCLUSIONS: Positive selection may explain the low risk in Canada, while the change from exclusion to inclusion may do the same in Israel. Given the high risks among migrants from developing countries in Europe, social exclusion may have a pathogenic role.

Performance of the quick SOFA in very old ICU patients admitted with sepsis.

BACKGROUND: The number of very elderly ICU patients (abbreviated to VOPs; ≥80 years) with sepsis increases. Sepsis was redefined in 2016 (sepsis 3.0) using the quick SOFA (qSOFA) score. Since then, multiple studies have validated qSOFA for prognostication in different patient categories, but the prognostic value in VOPs with sepsis is still unknown. METHODS: Retrospective cohort study including patients admitted to Dutch ICUs with sepsis, in the period 2012 to 2016, evaluating the outcome and the performance of qSOFA, an extended qSOFA model, SOFA, SAPS II, and APACHE IV for hospital mortality. RESULTS: 5969 patients were included, of which 935 VOPs. Crude hospital mortality rates were 19%, 28%, and 39% for patients aged 18-65, 65-80, and ≥80 years respectively. Discriminative performance of qSOFA for in-hospital mortality in VOPs was poor (AUC 0.596) and lower than that of SOFA, APACHE IV, and SAPS II (0.704, 0.722, and 0.780 respectively). A qSOFA model extended with several other characteristics (AUC 0.643) was non-inferior to the full SOFA, but still inferior to APACHE IV and SAPS II, for all age groups. The Hosmer-Lemeshow goodness-of-fit test showed non-significant p-values for all models. Accuracy for both qSOFA and the extended qSOFA was lower compared to APACHE IV and SAPS II (Brier scores 0.227, 0.223, 0.184, and 0.183 respectively). CONCLUSION: The qSOFA showed worse discriminative performance to predict mortality than SOFA, APACHE IV, and SAPS II in both VOPs and younger patients admitted with sepsis.

Emergency Department to ICU Time Is Associated With Hospital Mortality: A Registry Analysis of 14,788 Patients From Six University Hospitals in The Netherlands.

OBJECTIVES: Prolonged emergency department to ICU waiting time may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality. DESIGN, SETTING, AND PATIENTS: We conducted a retrospective observational cohort study using data from the Dutch quality registry National Intensive Care Evaluation. Adult patients admitted to the ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation IV probability) odds ratios of emergency department to ICU time on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30-day, and 90-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 14,788 patients were included. The median emergency department to ICU time was 2.0 hours (interquartile range, 1.3-3.3 hr). Emergency department to ICU time was correlated to adjusted hospital mortality (p < 0.002), in particular in patients with the highest Acute Physiology and Chronic Health Evaluation IV probability and long emergency department to ICU time quintiles: odds ratio, 1.29; 95% CI, 1.02-1.64 (2.4-3.7 hr) and odds ratio, 1.54; 95% CI, 1.11-2.14 (> 3.7 hr), both compared with the reference category (< 1.2 hr). For 30-day and 90-day mortality, we found similar results. However, emergency department to ICU time was not correlated to adjusted ICU mortality (p = 0.20). CONCLUSIONS: Prolonged emergency department to ICU time (> 2.4 hr) is associated with increased hospital mortality after ICU admission, mainly driven by patients who had a higher Acute Physiology and Chronic Health Evaluation IV probability. We hereby provide evidence that rapid admission of the most critically ill patients to the ICU might reduce hospital mortality.

Dispensing of psychotropic medication among 400,000 immigrants in The Netherlands.

PURPOSE: Previously, a high prevalence of certain psychiatric disorders was shown among non-Western immigrants. This study explores whether this results in more prescriptions for psychotropic medication. METHODS: Data on dispensing of medication among adults living in the four largest Dutch cities in 2013 were linked to demographic data from Statistics Netherlands. Incident (i.e., following no dispensing in 2010-2012) and prevalent dispensing among immigrants was compared to that among native Dutch (N = 1,043,732) and analyzed using multivariable Poisson and logistic regression. RESULTS: High adjusted Odds Ratios (ORadj) of prevalent and high Incidence Rate Ratios (IRRadj) of incident dispensing of antipsychotics were found among Moroccan (N = 115,455) and Turkish individuals (N = 105,460), especially among young Moroccan males (ORadj = 3.22 [2.99-3.47]). Among Surinamese (N = 147,123) and Antillean individuals (N = 41,430), slightly higher rates of dispensed antipsychotics were found and the estimates decreased after adjustment. The estimates for antipsychotic dispensing among the Moroccan and Turkish increased, following adjustment for household composition. Rates for antidepressant dispensing among Turkish and Moroccan subjects were high (Moroccans: ORadj = 1.74 [1.70-1.78]). Among Surinamese and Antillean subjects, the rates for antidepressant dispensing were low and the ORadj lagged behind the IRRadj (Surinamese: 0.69 [0.67-0.71] vs. 1.06 [1.00-1.13]). Similar results were found for anxiolytics. For ADHD medication, lower dispensing rates were found among all migrant groups. CONCLUSIONS: The findings agree with earlier reports of more mental health problems among Moroccan and Turkish individuals. Surinamese/Antillean individuals did not use psychotropic drugs at excess and discontinued antidepressants and anxiolytics earlier. The data strongly suggest under-treatment for ADHD in all ethnic minority groups.