With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal... Show moreWith a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor. Show less
Background: We systematically reviewed the literature to answer the following research questions: (1) Does interleukin 6 (IL-6) (receptor) antagonist therapy reduce mortality in coronavirus disease... Show moreBackground: We systematically reviewed the literature to answer the following research questions: (1) Does interleukin 6 (IL-6) (receptor) antagonist therapy reduce mortality in coronavirus disease 2019 (COVID-19) patients compared to patients not treated with IL-6 (receptor) antagonists; and (2) is there an increased risk of side effects in COVID-19 patients treated with IL-6 (receptor) antagonists compared to patients not treated with IL-6 (receptor) antagonists?Methods: We systematically searched PubMed, PMC PubMed Central, Medline, World Health Organization COVID-19 Database, Embase, Web of Science, Cochrane Library, Emcare, and Academic Search Premier (through 30 June 2020). Random effects meta-analysis was used to pool the risk ratios and risk differences of individual studies. Risk of bias was appraised using the Methodological Index for Non-randomized Studies (MINORS) checklist.Results: The search strategy retrieved 743 unique titles, of which 10 studies (all on tocilizumab [TCZ]) comprising 1358 patients were included. Nine of 10 studies were considered to be of high quality. Meta-analysis showed that the TCZ group had lower mortality than the control group. The risk ratio was 0.27 (95% confidence interval [CI], .12-.59) and the risk difference was 12% (95% CI, 4.6%-20%) in favor of the TCZ group. With only a few studies available, there were no differences observed regarding side effects.Conclusions: Our results showed that mortality was 12% lower for COVID-19 patients treated with TCZ compared with those not treated with TCZ. The number needed to treat was 11, suggesting that for every 11 (severe) COVID-19 patients treated with TCZ, 1 death is prevented. These results require confirmation by randomized controlled trials. Show less
BackgroundRecent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are... Show moreBackgroundRecent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with recurrent vascular events and death in patients with first-ever, mild to moderate ischemic stroke.Methods and ResultsWe used data from the PROSCIS-B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs-cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all-cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs-cTnT above upper reference limit, 39.2%). During a mean follow-up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all-cause death. The primary outcome occurred more often in patients with hs-cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3-3.3), with a dose-response relationship when the highest and lowest hs-cTnT quartiles were compared (15.2 versus 1.8 events per 100 person-years; adjusted hazard ratio, 4.8; 95% CI, 1.9-11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex.ConclusionsHs-cTnT is dose-dependently associated with an increased risk of recurrent vascular events and death within 3 years after first-ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs-cTnT for individualized risk stratification after stroke.RegistrationURL: ; Unique identifier: NCT01363856. Show less
Objectives To evaluate the postoperative complication and mortality rate following laparoscopic radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) in octogenarians.Patients and... Show moreObjectives To evaluate the postoperative complication and mortality rate following laparoscopic radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) in octogenarians.Patients and Methods We conducted a retrospective analysis comparing postoperative complication and mortality rates depending on age in a consecutive series of 1890 patients who underwent RARC with ICUD for bladder cancer between 2004 and 2018 in 10 European centres. Outcomes of patients aged <80 years and those aged >= 80 years were compared with regard to postoperative complications (Clavien-Dindo grading) and mortality rate. Cancer-specific mortality (CSM) and other-cause mortality (OCM) after surgery were calculated using the non-parametric Aalen-Johansen estimator.Results A total of 1726 patients aged <80 years and 164 aged >= 80 years were included in the analysis. The 30- and 90-day rate for high-grade (Clavien-Dindo grades III-V) complications were 15% and 21% for patients aged <80 years compared to 11% and 13% for patients aged >= 80 years (P = 0.2 and P = 0.03), respectively. In a multivariable logistic regression analysis adjusting for pre- and postoperative variables, age >= 80 years was not an independent predictor of high-grade complications (odds ratio 0.6, 95% confidence interval 0.3-1.1; P = 0.12). The non-cancer-related 90-day mortality was 2.3% for patients aged >= 80 years and 1.8% for those aged <80 years, respectively (P = 0.7). The estimated 12-month CSM and OCM rates for those aged <80 years were 8% and 3%, and for those aged >= 80 years, 15% and 8%, respectively (P = 0.009 and P < 0.001).Conclusions The minimally invasive approach to RARC with ICUD for bladder cancer in well-selected elderly patients (aged >= 80 years) achieved a tolerable high-grade complication rate; the 90-day postoperative mortality rate was driven by cancer progression and the non-cancer-related rate was equivalent to that of patients aged <80 years. However, an increased OCM rate in this elderly group after the first year should be taken into account. These results will support clinicians and patients when balancing cancer-related vs treatment-related risks and benefits. Show less
Czepiel, J.; Krutova, M.; Mizrahi, A.; Khanafer, N.; Enoch, D.A.; Patyi, M.; ... ; Garlicki, A. 2021
We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive,... Show moreWe aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were beta-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome. Show less
Simple SummaryA prognostic index for predicting survival of localized prostate cancer (PCa) up to 15 and 20 years was developed. The prognostic index performed well for predicting PCa survival... Show moreSimple SummaryA prognostic index for predicting survival of localized prostate cancer (PCa) up to 15 and 20 years was developed. The prognostic index performed well for predicting PCa survival among screened and non-screened men. The performance of the prediction model was superior to the European Association of Urology (EAU) risk groups as well as a modified cancer of prostate risk assessment (CAPRA) risk score. We further constructed a simplified risk score in an unscreened population, using the three most relevant predictors. The simplified risk score was applied to predict PCa survival at 10 years from diagnosis to provide more accurate risk estimation as the basis for decision making.We developed and validated a prognostic index to predict survival from prostate cancer (PCa) based on the Finnish randomized screening trial (FinRSPC). Men diagnosed with localized PCa (N = 7042) were included. European Association of Urology risk groups were defined. The follow-up was divided into three periods (0-3, 3-9 and 9-20 years) for development and two corresponding validation periods (3-6 and 9-15 years). A multivariable complementary log-log regression model was used to calculate the full prognostic index. Predicted cause-specific survival at 10 years from diagnosis was calculated for the control arm using a simplified risk score at diagnosis. The full prognostic index discriminates well men with PCa with different survival. The area under the curve (AUC) was 0.83 for both the 3-6 year and 9-15 year validation periods. In the simplified risk score, patients with a low risk score at diagnosis had the most favorable survival, while the outcome was poorest for the patients with high risk scores. The prognostic index was able to distinguish well between men with higher and lower survival, and the simplified risk score can be used as a basis for decision making. Show less
Background. Whether latent cytomegalovirus (CMV) infection in older adults has any substantial health consequences is unclear. Here, we sought associations between CMV-seropositivity and IgG titer... Show moreBackground. Whether latent cytomegalovirus (CMV) infection in older adults has any substantial health consequences is unclear. Here, we sought associations between CMV-seropositivity and IgG titer with all-cause and cardiovascular mortality in 5 longitudinal cohorts.Methods. Leiden Longevity Study, Prospective Study of Pravastatin in the Elderly at Risk, Longitudinal Study of Aging Danish Twins, and Leiden 85-plus Study were assessed at median (2.8-11.4 years) follow-up . Cox regression and random effects meta-analysis were used to estimate mortality risk dependent on CMV serostatus and/or IgG antibody titer, in quartiles after adjusting for confounders.Results. CMV-seropositivity was seen in 47%-79% of 10 122 white community-dwelling adults aged 59-93 years. Of these, 3519 had died on follow-up (579 from cardiovascular disease). CMV seropositivity was not associated with all-cause (hazard ratio [HR], 1.05; 95% confidence interval [CI], .97-1.14) or cardiovascular mortality (HR, 0.97; 95% CI, .83-1.13). Subjects in the highest CMV IgG quartile group had increased all-cause mortality relative to CMV-seronegatives (HR, 1.16; 95% CI, 1.04-1.29) but this association lost significance after adjustment for confounders (HR, 1.13; 95% CI, .99-1.29). The lack of increased mortality risk was confirmed in subanalyses.Conclusions. CMV infection is not associated with all-cause or cardiovascular mortality in white community-dwelling older adults. Show less
Background Treatment of patients with hemophilia has advanced over the past decades, but it is unknown whether this has resulted in a normal life expectancy in the Netherlands.Objective This... Show moreBackground Treatment of patients with hemophilia has advanced over the past decades, but it is unknown whether this has resulted in a normal life expectancy in the Netherlands.Objective This observational cohort study aimed to assess all-cause and cause-specific mortality in patients with hemophilia in the Netherlands between 2001 and 2018 and to compare mortality and life expectancy with previous survival assessments from 1973 onward.Patients/methods All 1066 patients with hemophilia who participated in a nationwide survey in 2001 were followed until July 2018.Results Information on 1031 individuals (97%) was available, of whom 142 (14%) deceased during follow-up. Compared with the general Dutch male population, mortality of patients with hemophilia was still increased (standardized mortality ratio: 1.4, 95% confidence interval: 1.2-1.7). Intracranial bleeding and malignancies were the most common causes of death. Estimated median life expectancy of patients with hemophilia was 77 years, 6 years lower than the median life expectancy of the general Dutch male population (83 years). Over the past 45 years, death rates of patients with hemophilia have consistently decreased, approaching the survival experience of the general population. Over the past decades, mortality due to human immunodeficiency virus and hepatitis C virus infections has decreased, death due to intracranial hemorrhages has increased, and death due to ischemic heart disease has remained consistently low over time.Conclusions Survival in patients with hemophilia in the Netherlands has improved over time but is still lower than that of the general population. Show less
Schroijen, M.A.; Diepen, M. van; Hamming, J.F.; Dekker, F.W.; Dekkers, O.M.; NECOSAD Study Grp 2020
Background: Survival among dialysis patients with diabetes mellitus (DM) is inferior to survival of non-diabetic dialysis patients, probably due to the higher prevalence of diabetes-related... Show moreBackground: Survival among dialysis patients with diabetes mellitus (DM) is inferior to survival of non-diabetic dialysis patients, probably due to the higher prevalence of diabetes-related comorbid conditions. One could hypothesize that these comorbid conditions also contribute to a decreased survival after amputation in diabetic patients compared with non-diabetic patients on dialysis.Methods: Data were collected from the Netherlands Cooperative Study on the Adequacy of Dialysis, a multicentre, prospective cohort study in which new patients with end-stage renal disease were monitored until transplantation or death. Amputation rates (incident cases) were calculated in patients with and without DM. The primary endpoint was all-cause survival after first amputation during dialysis therapy in diabetic patients compared with non-diabetic dialysis patients with an amputation. This was formally assessed using interaction analysis (Poisson regression).Results: During follow-up (mean duration 2.9 years), 50 of the 413 diabetic patients had a new amputation (12.1%), compared with 20 of 1553 non-diabetic patients (1.2%). Amputation rates/1000 person-years were 47.9 [95% confidence interval (CI) 36.3-63.2] and 4.1 (95% CI 2.7-6.4), respectively, for diabetic patients and non-diabetic patients. Amputation increased mortality risk more than 4-fold in patients without diabetes [hazard ratio (HR) 4.6 (95% CI 2.8-7.6)] as well as in patients with diabetes [HR 4.6 (95% CI 3.3-6.4)]. No formal interaction between diabetes and amputation was found (P = 0.12).Conclusions: Amputation in dialysis patients is associated with a 4-fold increased mortality risk; this mortality risk was similar for diabetes and non-diabetes patients. Importantly, the risk for amputation is 10-fold higher in DM compared with non-diabetic dialysis patients. Show less
Monahan, R.; Fronczek, R.; Eikenboom, J.; Middelkoop, H.; Beaart-van de Voorde, L.; Terwindt, G.; ... ; Steup-Beekman, M. 2020
ObjectiveWe aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018... Show moreObjectiveWe aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018.MethodsPatients visiting the tertiary referral NPSLE clinic of the Leiden University Medical Center were included. NP symptoms were attributed to SLE requiring treatment (major NPSLE) or to other and mild causes (minor/non-NPSLE). Municipal registries were checked for current status (alive/deceased). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using data from the Dutch population. Rate ratio (RR) and 95% CI were calculated using direct standardization to compare mortality between major NPSLE and minor/non-NPSLE.Results351 patients were included and 149 patients were classified as major NPSLE (42.5%). Compared with the general population, mortality was increased in major NPSLE (SMR 5.0 (95% CI: 2.6-8.5)) and minor/non-NPSLE patients (SMR 3.7 (95% CI: 2.2-6.0)). Compared with minor/non-NPSLE, mortality was similar in major NPSLE patients (RR: 1.0 (95% CI: 0.5-2.0)). Cause-specific mortality rates demonstrated an increased risk of death due to infections in both groups, whereas death due to cardiovascular disease was only increased in minor/non-NPSLE patients.ConclusionMortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients. Show less
ObjectiveWe aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018... Show moreObjectiveWe aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018.MethodsPatients visiting the tertiary referral NPSLE clinic of the Leiden University Medical Center were included. NP symptoms were attributed to SLE requiring treatment (major NPSLE) or to other and mild causes (minor/non-NPSLE). Municipal registries were checked for current status (alive/deceased). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using data from the Dutch population. Rate ratio (RR) and 95% CI were calculated using direct standardization to compare mortality between major NPSLE and minor/non-NPSLE.Results351 patients were included and 149 patients were classified as major NPSLE (42.5%). Compared with the general population, mortality was increased in major NPSLE (SMR 5.0 (95% CI: 2.6-8.5)) and minor/non-NPSLE patients (SMR 3.7 (95% CI: 2.2-6.0)). Compared with minor/non-NPSLE, mortality was similar in major NPSLE patients (RR: 1.0 (95% CI: 0.5-2.0)). Cause-specific mortality rates demonstrated an increased risk of death due to infections in both groups, whereas death due to cardiovascular disease was only increased in minor/non-NPSLE patients.ConclusionMortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients. Show less
Background: Subclinical and overt thyroid dysfunction is easily detectable, often modifiable, and, in younger age groups, has been associated with clinically relevant outcomes. Robust associations... Show moreBackground: Subclinical and overt thyroid dysfunction is easily detectable, often modifiable, and, in younger age groups, has been associated with clinically relevant outcomes. Robust associations in very old persons, however, are currently lacking. This study aimed to investigate the associations between (sub-)clinical thyroid dysfunction and disability in daily living, cognitive function, depressive symptoms, physical function, and mortality in people aged 80 years and older.Methods: Four prospective cohorts participating in the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included. We performed a two-step individual participant data meta-analysis on source data from community-dwelling participants aged 80 years and older from the Netherlands, New Zealand, United Kingdom, and Japan. Outcome measures included disability in daily living (disability in activities of daily living [ADL] questionnaires), cognitive function (Mini-Mental State Examination [MMSE]), depressive symptoms (Geriatric Depression Scale [GDS]), physical function (grip strength) at baseline and after 5 years of follow-up, and all-cause five-year mortality.Results: Of the total 2116 participants at baseline (mean age 87 years, range 80-109 years), 105 participants (5.0%) were overtly hypothyroid, 136 (6.4%) subclinically hypothyroid, 1811 (85.6%) euthyroid, 60 (2.8%) subclinically hyperthyroid, and 4 (0.2%) overtly hyperthyroid. Participants with thyroid dysfunction at baseline had nonsignificantly different ADL scores compared with euthyroid participants at baseline and had similar MMSE scores, GDS scores, and grip strength. There was no difference in the change of any of these functional measures in participants with thyroid dysfunction during five years of follow-up. Compared with the euthyroid participants, no 5-year survival differences were identified in participants with overt hypothyroidism (hazard ratio [HR] 1.0, 95% confidence interval [CI 0.6-1.6]), subclinical hypothyroidism (HR 0.9 [CI 0.7-1.2]), subclinical hyperthyroidism (HR 1.1 [CI 0.8-1.7]), and overt hyperthyroidism (HR 1.5 [CI 0.4-5.9]). Results did not differ after excluding participants using thyroid-influencing medication.Conclusions: In community-dwelling people aged 80 years and older, (sub-)clinical thyroid dysfunction was not associated with functional outcomes or mortality and may therefore be of limited clinical significance. Show less
Background:It is unknown if beta-blockers reduce mortality/morbidity in patients with heart failure (HF) and advanced chronic kidney disease (CKD), a population underrepresented in HF trials... Show moreBackground:It is unknown if beta-blockers reduce mortality/morbidity in patients with heart failure (HF) and advanced chronic kidney disease (CKD), a population underrepresented in HF trials.Methods:Observational cohort of HF patients with advanced CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m(2)) from the Swedish Heart Failure Registry between 2001 and 2016. We first explored associations between beta-blocker use, 5-year death, and the composite of cardiovascular death/HF hospitalization among 3775 patients with HF with reduced ejection fraction (HFrEF) and advanced CKD. We compared observed hazards with those from a control cohort of 15 346 patients with HFrEF and moderate CKD (estimated glomerular filtration rate <60-30 mL/min per 1.73 m(2)), for whom beta-blocker trials demonstrate benefit. Second, we explored outcomes associated to beta-blocker among advanced CKD participants with preserved (HFpEF; N=2009) and midrange ejection fraction (HFmrEF; N=1514).Results:During a median follow-up of 1.3 years, 2012 patients had a subsequent HF hospitalization, and 2849 died in the HFrEF cohort, of which 2016 died due to cardiovascular causes. Among patients with HFrEF, beta-blocker use was associated with lower risk of death (adjusted hazard ratio 0.85 [95% CI, 0.75-0.96]) and cardiovascular mortality/HF hospitalization (0.87 [0.77-0.98]) compared with nonuse. The magnitude of the associations was similar to that observed for HFrEF patients with moderate CKD. Conversely, no significant association was observed for beta-blocker users in advanced CKD with HFpEF (death: 0.88 [0.77-1.02], cardiovascular mortality/HF hospitalization: 1.05 [0.90-1.23]) or HFmrEF (death: 0.95 [0.79-1.14], cardiovascular mortality/HF hospitalization: 1.09 [0.90-1.31]).Conclusions:In HFrEF patients with advanced CKD, the use of beta-blockers was associated with lower morbidity and mortality. Although inconclusive due to limited power, these benefits were not observed in similar patients with HFpEF or HFmrEF. Show less
Valburg, M.K. van; Termorshuizen, F.; Brinkman, S.; Abdo, W.F.; Bergh, W.M. van den; Horn, J.; ... ; Arbous, M.S. 2020
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... Show moreObjectives: 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. Show less
Simple Summary Adrenocortical carcinoma is a rare and aggressive cancer. Great variability in clinical course is observed, ranging from patients with extreme long survival to aggressive tumors with... Show moreSimple Summary Adrenocortical carcinoma is a rare and aggressive cancer. Great variability in clinical course is observed, ranging from patients with extreme long survival to aggressive tumors with prompt fatal outcome. This heterogeneity in survival makes it complicated to tailor treatment strategies for an individual patient. Therefore we sought to identify prognostic factors associated with ACC specific mortality. We analyzed the data of 160 ACC patients and developed a clinical prediction model including age, modified European Network for the Study of Adrenal Tumors (mENSAT) stage, and radical resection. This easy-to-use prediction model for ACC-specific mortality has the potential to guide clinical decision making if externally validated. Adrenocortical carcinoma (ACC) has an incidence of about 1.0 per million per year. In general, survival of patients with ACC is limited. Predicting survival outcome at time of diagnosis is a clinical challenge. The aim of this study was to develop and internally validate a clinical prediction model for ACC-specific mortality. Data for this retrospective cohort study were obtained from the nine centers of the Dutch Adrenal Network (DAN). Patients who presented with ACC between 1 January 2004 and 31 October 2013 were included. We used multivariable Cox proportional hazards regression to compute the coefficients for the prediction model. Backward stepwise elimination was performed to derive a more parsimonious model. The performance of the initial prediction model was quantified by measures of model fit, discriminative ability, and calibration. We undertook an internal validation step to counteract the possible overfitting of our model. A total of 160 patients were included in the cohort. The median survival time was 35 months, and interquartile range (IQR) 50.7 months. The multivariable modeling yielded a prediction model that included age, modified European Network for the Study of Adrenal Tumors (mENSAT) stage, and radical resection. The c-statistic was 0.77 (95% Confidence Interval: 0.72, 0.81), indicating good predictive performance. We developed a clinical prediction model for ACC-specific mortality. ACC mortality can be estimated using a relatively simple clinical prediction model with good discriminative ability and calibration. Show less
The purpose was to compare time-based vs anti-Xa-based anticoagulation strategies in patients on ECMO. We conducted a systematic review and meta-analysis using multiple electronic databases and... Show moreThe purpose was to compare time-based vs anti-Xa-based anticoagulation strategies in patients on ECMO. We conducted a systematic review and meta-analysis using multiple electronic databases and included studies from inception to July 19, 2019. The proportion of bleeding, thrombosis, and mortality were evaluated. Twenty-six studies (2,086 patients) were included. Bleeding occurred in 34.2% (95%CI 25.1;43.9) of the patients with anti-Xa-based versus 41.6% (95%CI 24.9;59.4) of the patients with time-based anticoagulation strategies. Thrombosis occurred in 32.6% (95%CI 19.1;47.7) of the patients with anti-Xa-based versus 38.4% (95%CI 22.2;56.1) of the patients with time-based anticoagulation strategies. And mortality rate was 35.4% (95%CI 28.9;42.1) of the patients with anti-Xa-based versus 42.9% (95%CI 36.9;48.9) of the patients with time-based anticoagulation strategies. Among the seven studies providing results from both anticoagulation strategies, significantly fewer bleeding events occurred in the anti-Xa-based anticoagulation strategy (adjusted OR 0.49 (95%CI 0.32;0.74),p < 0.001) and a significantly lower mortality rate (adjusted OR 0.61 (95%CI 0.40;0.95),p = 0.03). There was no significant difference in thrombotic events (adjusted OR 0.91 (95%CI 0.56;1.49),p = 0.71). In these seven observational studies, only a small fraction of the patients were adults, and data were insufficient to analyze the effect of the type of ECMO. In this meta-analysis of observational studies of patients on ECMO, an anti-Xa-based anticoagulation strategy, when compared to a time-based strategy, was associated with fewer bleeding events and mortality rate, without an increase in thrombotic events. Show less
Background The Hestia criteria can be used to select pulmonary embolism (PE) patients for outpatient treatment. The subjective Hestia criterion "medical/social reason for admission" allows the... Show moreBackground The Hestia criteria can be used to select pulmonary embolism (PE) patients for outpatient treatment. The subjective Hestia criterion "medical/social reason for admission" allows the treating physician to consider any patient-specific circumstances in the final management decision. It is unknown how often and why this criterion is scored. Methods This is a patient-level post hoc analysis of the combined Hestia and Vesta studies. The main outcomes were the frequency of all scored Hestia items in hospitalized patients and the explicit reason for scoring the subjective criterion. Hemodynamic parameters and computed tomography-assessed right ventricular (RV)/left ventricular (LV) ratio of those only awarded with the subjective criterion were compared with patients treated at home. Results From the 1,166 patients screened, data were available for all 600 who were hospitalized. Most were hospitalized to receive oxygen therapy (45%); 227 (38%) were only awarded with the subjective criterion, of whom 51 because of "intermediate to intermediate-high risk PE." Compared with patients with intermediate risk PE (RV/LV ratio > 1.0) treated at home (179/566, 32%), hospitalized patients with only the subjective criterion had a higher mean RV/LV ratio (mean difference +0.30, 95% confidence interval [CI] 0.19-0.41) and a higher heart rate (+18/min, 95% CI 10-25). No relevant differences were observed for other hemodynamic parameters. Conclusion The most frequent reason for hospital admission was oxygen therapy. In the decision to award the subjective criterion as sole argument for admission, the severity of the RV overload and resulting hemodynamic response of the patient was taken into account rather than just abnormal RV/LV ratio. Show less
Mourits, R.J.; Berg, N. van den; Rodriguez-Girondo, M.; Mandemakers, K.; Slagboom, P.E.; Beekman, M.; Janssens, A.A.P.O. 2020
Studies have shown that long-lived individuals seem to pass their survival advantage on to their offspring. Offspring of long-lived parents had a lifelong survival advantage over individuals... Show moreStudies have shown that long-lived individuals seem to pass their survival advantage on to their offspring. Offspring of long-lived parents had a lifelong survival advantage over individuals without long-lived parents, making them more likely to become long-lived themselves. We test whether the survival advantage enjoyed by offspring of long-lived individuals is explained by environmental factors. 101,577 individuals from 16,905 families in the 1812-1886 Zeeland cohort were followed over time. To prevent that certain families were overrepresented in our data, disjoint family trees were selected. Offspring was included if the age at death of both parents was known. Our analyses show that multiple familial resources are associated with survival within the first 5 years of life, with stronger maternal than paternal effects. However, between ages 5 and 100 both parents contribute equally to offspring's survival chances. After age 5, offspring of long-lived fathers and long-lived mothers had a 16-19% lower chance of dying at any given point in time than individuals without long-lived parents. This survival advantage is most likely genetic in nature, as it could not be explained by other, tested familial resources and is transmitted equally by fathers and mothers. Show less
Chao, A.; Spiegelman, D.; Khan, S.; Walsh, F.; Mazibuko, S.; Pasipamire, M.; ... ; Okello, V. 2020
Objectives Current WHO guidelines recommend the treatment of all HIV-infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others... Show moreObjectives Current WHO guidelines recommend the treatment of all HIV-infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others. MaxART is the first implementation trial of this strategy embedded within a government-managed health system, and assesses mortality as a secondary outcome. Because primary findings strongly supported scale-up of the 'treat all' strategy (hereafter Treat All), this analysis examines mortality as an additional indicator of its impact.Methods MaxART was conducted in 14 Eswatinian health clinics through a clinic-based stepped-wedge design, by transitioning clinics from then-national standard of care (SoC) to the Treat All intervention. All-cause, disease-related, and HIV-related mortality were analysed using the Cox proportional hazards model, censoring SoC participants at clinic transition. Median follow-up time among study participants was 292 days. There were 36/2034 deaths in SoC (1.77%) and 49/1371 deaths in Treat All (3.57%).Results Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and Treat All interventions, respectively, the multivariable-adjusted 12-month all-cause mortality rates were 1.42% [95% confidence interval (CI): 0.66-2.17] and 1.60% (95% CI: 0.78-2.40), disease-related mortality rates were 1.02% (95% CI: 0.40-1.64) and 1.10% (95% CI: 0.46-1.73), and HIV-related mortality rates were 1.03% (95% CI: 0.40-1.65) and 0.99% (95% CI: 0.40-1.58). Treat All had no impact on all-cause [hazard ratio (HR) = 1.12, 95% CI: 0.58-2.18, P = 0.73], disease-related (HR = 1.04, 95% CI: 0.52-2.11, P = 0.90), or HIV-related mortality (HR = 0.93, 95% CI: 0.46-1.87, P = 0.83).Conclusion There was no immediate benefit of the Treat All strategy on mortality, nor evidence of harm. Longer follow-up of participants is needed to establish long-term consequences. Show less
Objectives Older adults with psychiatric disorders have a substantially lower life expectancy than age-matched controls. Knowledge of risk factors may lead to targeting treatment and interventions... Show moreObjectives Older adults with psychiatric disorders have a substantially lower life expectancy than age-matched controls. Knowledge of risk factors may lead to targeting treatment and interventions to reduce this gap in life expectancy. In this study, we investigated whether frailty independently predicts mortality in older patients following an acute admission to a geriatric psychiatry hospital.Methods Clinical cohort study with a 5-year follow-up of 120 older patients admitted to a psychiatric hospital between February 2009 and September 2010. On admission, we assessed frailty with a frailty index (FI). We applied Cox regression analyses with time to death as the dependent variable, to examine whether the FI was a predictor for mortality, adjusted for age, sex, level of education, multimorbidity (Cumulative Illness Rating Scale for Geriatrics, CIRS-G scores), functional status (Barthel Index), neuropsychiatric symptoms (NPS), and severity of psychiatric symptoms at admission (Clinical Global Impressions Scale of Severity).Results Of the 120 patients, 63 (53%) patients were frail (FI >= 0.25), and 59 (49%) had died within 5 years. The FI predicted mortality with a hazard ratio (HR) of 1.78 (95% CI, 1.06-2.98) per 0.1 point increase, independent of the covariates. Co-morbidity measured by the CIRS-G and functional status measured by the Barthel Index were not significantly associated.Conclusions Frailty was a strong predictor of mortality, independent of age, gender, multimorbidity, and functional status. This implies that frailty may be helpful in targeting inpatient psychiatric treatment and aftercare according to patients' life expectancy. Show less
