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.

Influenza Season and Outcome After Elective Cardiac Surgery: An Observational Cohort Study.

BACKGROUND: An asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral infection before surgery or vaccination could reduce the number of these pulmonary complications. The aim of this study was to investigate the association between influenzalike illness (ILI) seasons and prolonged mechanical ventilation and inhospital mortality in a Dutch cohort of adult elective cardiac surgery patients. METHODS: Cardiac surgery patients who were admitted to the intensive care unit between January 1, 2014, and February 1, 2020, were included. The primary endpoint was the duration of invasive mechanical ventilation in the ILI season compared with baseline season. Secondary endpoints were the median Pao2 to fraction of inspired oxygen ratio on days 1, 3, and 7 and postoperative inhospital mortality. RESULTS: A total of 42,277 patients underwent cardiac surgery, 12,994 (30.7%) in the ILI season, 15,843 (37.5%) in the intermediate season, and 13,440 (31.8%) in the baseline season. No hazard rates indicative of a longer duration of invasive mechanical ventilation during the ILI season were found. No differences were found for the median Pao2 to fraction of inspired oxygen ratio between seasons. However, inhospital mortality was higher in the ILI season compared with baseline season (odds ratio 1.67; 95% CI, 1.14-2.46). CONCLUSIONS: Patients undergoing cardiac surgery during the ILI season were at increased risk of inhospital mortality compared with patients in the baseline season. No evidence was found that this difference is caused by direct postoperative pulmonary complications.

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.

The impact of ethnic density on dispensing of antipsychotic and antidepressant medication among immigrants in the Netherlands.

PURPOSE: A higher own-group ethnic density in the area of residence is often associated with a lower risk for psychotic disorder. For common mental disorders the evidence is less convincing. This study explores whether these findings are mirrored in data on dispensing of antipsychotics and antidepressants. METHODS: Health insurance data on dispensed medication among all adults living in the four largest Dutch cities were linked to demographic data from Statistics Netherlands. Dispensing of antipsychotics and antidepressants in 2013 was analyzed in relation to the proportion of the own ethnic group in the neighborhood. RESULTS: Higher own-group ethnic density was associated with lower dispensing of antipsychotics among the Moroccan-Dutch (N = 115,455), after adjusting for age, gender, and SES of the neighborhood (ORadj for the highest vs. the lowest density quintile = 0.72 [0.66-0.79]). However, this association vanished after adjustment for household composition (ORadj = 0.93 [0.85-1.03]). Similar results were found for the Turkish-Dutch (N = 105,460) (ORadj = 0.86 [0.76-0.96] and 1.05 [0.94-1.18]). For those of Surinamese (N = 147,123) and Antillean origin (N = 41,430), in contrast, the association between ethnic density and lower risk remained after each adjustment (P < 0.001). For antidepressants, a negative association with own-group ethnic density was consistently found for those of Antillean origin (ORadj = 0.62 [0.52-0.74]) only. CONCLUSION: These data on dispensing of psychomedication confirm the ethnic density hypothesis for psychosis alongside earlier equivocal findings for other mental disorders. The negative association between own-group ethnic density and dispensing of antipsychotics among the Moroccan- and Turkish-Dutch may be explained, at least in part, by a favourable household composition (i.e., living in a family) in high-density neighborhoods.

Somatic Care with a Psychotic Disorder. Lower Somatic Health Care Utilization of Patients with a Psychotic Disorder Compared to Other Patient Groups and to Controls Without a Psychiatric Diagnosis.

Patients with non-affective psychotic disorders (NAPD) face higher risk of somatic problems and early natural death compared to the general population. Therefore, treatment guidelines for schizophrenia and psychosis stress the importance of monitoring somatic risk factors. This study examined somatic Health Care utilization (HCu) of patients with NAPD compared to non-psychiatric controls and patients with depression, anxiety or bipolar disorders using a large Health Insurance database. Results show lower specialist somatic HCu of patients with NAPD compared to matched controls and also lower percentages for prescribed somatic medication and general practitioner consultations for patients aged ≥60 years and after longer illness duration.

Cause-specific mortality among patients with psychosis: disentangling the effects of age and illness duration.

BACKGROUND: There is a large mortality gap between patients with a nonaffective psychotic disorder and those in the general population, is associated with both natural and nonnatural death causes. OBJECTIVE: This study aims to assess whether mortality risks vary for different causes of death according to the duration since diagnosis and age in a large sample of patients with nonaffective psychotic disorder. METHODS: Data of patients with nonaffective psychotic disorder (n = 12,580) from 3 Dutch psychiatric registers were linked to the cause of death register of Statistics Netherlands and compared with personally matched controls (n = 124,143) from the population register. Death rates were analyzed by duration since the date of the registered diagnosis of the (matched) patient and their age using a Poisson model. RESULTS: Among patients, the rates of all-cause death decreased with longer illness duration. This was explained by lower suicide rates. For example, among those between 40 and 60 years of age, the rate ratios (RR) of suicide during 2-5 and > 5 years were 0.52 and 0.46 (p = 0.002), respectively, when compared with the early years after diagnosis. Compared with controls, patients experienced higher rates of natural death causes during all stages and in all age categories, rate ratios 2.35-5.04; p < 0.001-0.025. There was no increase in these rate ratios with increasing duration or increasing age for patients when compared with controls. CONCLUSIONS: The high risk of natural death causes among patients with nonaffective psychotic disorder is already present at a comparatively young age. This suggests caution in blaming antipsychotics or the accumulating effects of adverse lifestyle factors for premature death. It is better to proactively monitor and treat somatic problems from the earliest disease stages onward.

Cancer mortality in patients with psychiatric diagnoses: a higher hazard of cancer death does not lead to a higher cumulative risk of dying from cancer.

PURPOSE: Both increased as well as decreased cancer mortality among psychiatric patients has been reported, but competing death causes were not included in the analyses. This study aims to investigate whether observed cancer mortality in patients with psychiatric disorders might be biased by competing death causes. METHOD: In this retrospective cohort study on data from the Psychiatric Case Register Middle Netherlands linked to the death register of Statistics Netherlands, the risk of cancer death among patients with schizophrenia (N = 4,590), bipolar disorder (N = 2,077), depression (N = 15,130) and their matched controls (N = 87,405) was analyzed using a competing risk model. RESULTS: Compared to controls, higher hazards of cancer death were found in patients with schizophrenia (HR = 1.61, 95 % CI 1.26-2.06), bipolar disorder (HR = 1.20, 95 % CI 0.81-1.79) and depression (HR = 1.26, 95 % CI 1.10-1.44). However, the HRs of death due to suicide and other death causes were more elevated. Consequently, among those who died, the 12-year cumulative risk of cancer death was significantly lower. CONCLUSIONS: Our analysis shows that, compared to the general population, psychiatric patients are at higher risk of dying from cancer, provided that they survive the much more elevated risks of suicide and other death causes.

A comorbid anxiety disorder does not result in an excess risk of death among patients with a depressive disorder.

BACKGROUND: Several studies have demonstrated increased mortality associated with depression and with anxiety. Mortality due to comorbidity of two mental disorders may be even more increased. Therefore, we investigated the mortality among patients with depression, with anxiety and with both diagnoses. METHODS: By linking the longitudinal Psychiatric Case Register Middle-Netherlands, which contains all patients of psychiatric services in the Utrecht region, to the death register of Statistics Netherlands, hazard ratio's of death were estimated overall and for different categories of death causes separately. RESULTS: We found an increased risk of death among patients with an anxiety disorder (N=6919): HR=1.45 (95%CI: 1.25-1.69), and among patients with a depression (N=14,778): HR=1.83, (95%CI: 1.72-1.95), compared to controls (N=103,824). The hazard ratios among both disorders combined (N=4260) were similar to those with only a depression: HR=1.91, (95% CI: 1.64-2.23). Among patients with a depression, mortality across all important disease-related categories of death causes (neoplasms, cardiovascular, respiratory, and other diseases) and due to suicide was increased, without an excess mortality in case of comorbid anxiety. LIMITATIONS: The presented data are restricted to broad categories of patients in specialist services. No data on behavioral or intermediate factors were available. CONCLUSIONS: Although anxiety is associated with an increased risk of death, the presence of anxiety as comorbid disorder does not give an additional increase in the risk of death among patients with a depressive disorder. The increased mortality among patients with depression is not restricted to suicide and cardiovascular diseases, but associated with a broad range of death causes.

Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials.

The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%.

Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study.

PURPOSE: For several decades, the treatment of elderly patients with multiple myeloma (MM) has consisted of melphalan and prednisone (MP). The Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) investigated the efficacy of thalidomide added to MP (MP-T) in a randomized phase III trial. The objective of this study was to investigate the efficacy, toxicity, and effects on quality of life of MP-T. PATIENTS AND METHODS: A randomized phase III trial compared standard MP with MP-T (thalidomide 200 mg/d) in newly diagnosed patients with multiple myeloma older than age 65 years. Maintenance therapy with thalidomide 50 mg/d was administered to patients after MP-T until relapse. The primary end point was event-free survival (EFS); response rate, overall survival (OS), and progression-free survival (PFS) were secondary end points. RESULTS: An intent-to-treat analysis of 333 evaluable patients showed significantly higher response rates in MP-T-treated patients compared with MP-treated patients a response (> or = partial response: 66% v 45%, respectively; P < .001; and > or = very good partial response [VGPR]: 27% v 10%, respectively; P < .001). EFS was 13 months with MP-T versus 9 months with MP (P < .001). OS was 40 months with MP-T versus 31 months with MP (P = .05). CONCLUSION: This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM. MP-T also results in a better EFS, PFS, and OS.

Sunlight exposure and (sero)prevalence of epidermodysplasia verruciformis-associated human papillomavirus.

Ultraviolet radiation (UVR) is associated with an increased risk of squamous cell carcinoma (SCC), which is in part due to immunomodulation. In addition, human papilloma virus (HPV), especially the epidermodysplasia verruciformis (EV)-associated types, may be involved. In view of the capacity of UVR to impair host resistance to infections, we investigated the relationship between solar exposure and the prevalence of cutaneous HPV. In a case-control study on skin cancer (320 controls and 156 patients) a lifetime-retrospective questionnaire on sun exposure was administered. The presence of DNA of HPV types 5, 8, 15, 20, 24, and 38 in plucked eyebrow hair and type-specific seroreactivity were assessed and analyzed in relation to estimated exposure. Sunburn episodes in the past, especially at age 13-20 y, appeared to be associated with an enhanced risk of EV-HPV DNA positivity. In contrast, a higher lifetime sun exposure was associated with a lower risk of HPV infection. These results indicate that UVR at erythematogenic doses increases the risk of EV-HPV infection, possibly due to impaired host resistance to HPV and/or a direct effect of UVR on viral replication. The favorable association between lifetime sun exposure and HPV prevalence, however, underscores the enigmatic role of HPV in skin carcinogenesis.

Exposure to solar ultraviolet radiation in young Dutch children: assessment by means of a 6-week retrospective questionnaire.

We designed a 6-week retrospective questionnaire on sunlight exposure. Estimation of the short-term exposure to sunlight is important for observational human studies concerning the effects of ultraviolet radiation (UVR) on the human immune system and related resistance to infections. This questionnaire was given to the parents of 1672 1-year-old children in the Netherlands who participated in a birth cohort study. We evaluated the questionnaire and estimated the personal 6-week cumulative exposure to solar UVR. Only 910 questionnaires (54.4%) were filled out completely and consistently. This suggests that reporting data on children's outdoor exposure, even for the recent past, is often difficult. The data from these questionnaires indicated that the crude number of reported outdoor hours was enough to obtain a relative estimate of the individual exposure to ambient UVR, but that weighting for the effect of clothing was essential for the classification of the systemic UVR dosage received. Sunny weeks in the Netherlands in 1998, as were established by independent measurements of the levels of ambient UVR, vacations abroad, and sunburn, were associated with a comparatively high mean estimated exposure. These results support the suitability of the questionnaire for classifying the participants with respect to their short-term exposure to solar UVR.