Epidemiology of Renal Replacement Therapy for Critically Ill Patients across Seven Health Jurisdictions.

INTRODUCTION: Acute kidney injury (AKI) requiring treatment with renal replacement therapy (RRT) is a common complication after admission to an intensive care unit (ICU) and is associated with significant morbidity and mortality. However, the prevalence of RRT use and the associated outcomes in critically patients across the globe are not well described. Therefore, we describe the epidemiology and outcomes of patients receiving RRT for AKI in ICUs across several large health system jurisdictions. METHODS: Retrospective cohort analysis using nationally representative and comparable databases from seven health jurisdictions in Australia, Brazil, Canada, Denmark, New Zealand, Scotland, and the USA between 2006 and 2023, depending on data availability of each dataset. Patients with a history of end-stage kidney disease receiving chronic RRT and patients with a history of renal transplant were excluded. RESULTS: A total of 4,104,480 patients in the ICU cohort and 3,520,516 patients in the mechanical ventilation cohort were included. Overall, 156,403 (3.8%) patients in the ICU cohort and 240,824 (6.8%) patients in the mechanical ventilation cohort were treated with RRT for AKI. In the ICU cohort, the proportion of patients treated with RRT was lowest in Australia and Brazil (3.3%) and highest in Scotland (9.2%). The in-hospital mortality for critically ill patients treated with RRT was almost fourfold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37 to 65%. CONCLUSION: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests that differences in access to and provision of this therapy are contributing factors.

Acute Kidney Injury Duration and 20-Year Risks of CKD and Cardiovascular Disease.

Introduction: Acute kidney injury (AKI) is associated with chronic kidney disease (CKD) and cardiovascular disease (CVD); however, it is unclear whether AKI duration affects the long-term risks of CKD and CVD. Therefore, we performed a population-based cohort study examining the associations between AKI duration and CKD and CVD. Methods: We identified patients with laboratory-recorded AKI in Denmark from 1990 through 2018. AKIs were categorized as rapid reversal AKI (≤48 hours), persistent AKI (2-7 days), and acute kidney disease (AKD) (>7 days). We estimated 20-year risks and adjusted hazard ratios (aHRs) of incident CKD and CVD. Results: The study comprised 169,582 patients with AKI, with 100,478 and 76,838 included in the analysis of CKD and CVD, respectively. The 20-year risks of CKD were 26.3%, 29.5%, and 28.7% for rapid reversal AKI, persistent AKI, and AKD, respectively. Compared with rapid reversal AKI, aHRs were 1.13 (95% confidence interval [CI], 1.08-1.19) for persistent AKI and 1.36 (95% CI, 1.30-1.41) for AKD. Risks and rates of overall CVD were similar for rapid reversal AKI, persistent AKI, and AKD. However, persistent AKI was associated with a slightly increased aHR of heart failure (1.09; 95% CI, 1.02-1.16), and aHRs of heart failure, ischemic heart disease, and peripheral artery disease were slightly increased for AKD (1.09 [95% CI, 1.03-1.15], 1.11 [95% CI, 1.03-1.19], and 1.10 [95% CI, 1.02-1.17], respectively). Conclusion: AKI duration was associated with development of CKD, but not overall CVD; however, rates of heart failure, ischemic heart disease, and peripheral artery disease increased slightly with AKI duration.

Risk factor analysis for a rapid progression of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a growing global health concern. Identifying individuals in routine clinical care with new-onset CKD at high risk of rapid progression of the disease is imperative to guide allocation of prophylactic interventions, but community-based data are limited. We aimed to examine the risk of rapid progression, kidney failure, hospitalization and death among adults with incident CKD stage G3 and to clarify the association between predefined risk markers and rapid CKD progression. METHODS: Using plasma creatinine measurements for the entire Danish population from both hospitals and primary care, we conducted a nationwide, population-based cohort study, including adults in Denmark with incident CKD stage G3 in 2017-2020. We estimated 3-year risks of rapid progression (defined by a confirmed decline in estimated glomerular filtration rate of ≥5 mL/min/1.73 m2/year), kidney failure, all-cause hospitalization and death. To examine risk markers, we constructed a heat map showing the risk of rapid progression based on predefined markers: albuminuria, sex, diabetes and hypertension/cardiovascular disease. RESULTS: Among 133 443 individuals with incident CKD stage G3, the 3-year risk of rapid progression was 14.6% [95% confidence interval (CI) 14.4-14.8]. The 3-year risks of kidney failure, hospitalization and death were 0.3% (95% CI 0.3-0.4), 53.3% (95% CI 53.0-53.6) and 18.1% (95% CI 17.9-18.4), respectively. In the heat map, the 3-year risk of rapid progression ranged from 7% in females without albuminuria, hypertension/cardiovascular disease or diabetes, to 46%-47% in males and females with severe albuminuria, diabetes and hypertension/cardiovascular disease. CONCLUSION: This population-based study shows that CKD stage G3 is associated with considerable morbidity in a community-based setting and underscores the need for optimized prophylactic interventions among such patients. Moreover, our data highlight the potential of using easily accessible markers in routine clinical care to identify individuals who are at high risk of rapid progression.

Recovery of kidney function after acute kidney disease-a multi-cohort analysis.

BACKGROUND: There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18. METHODS: We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts. RESULTS: There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes. CONCLUSION: Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.

Preadmission morbidity and healthcare utilization among older adults with potentially avoidable hospitalizations: a Danish case-control study.

PURPOSE: Examine preadmission diagnoses, medication use, and preadmission healthcare utilization among older adults prior to first potentially avoidable hospitalizations. METHODS: A nationwide population-based case-control study using Danish healthcare data. All Danish adults aged ≥ 65 years who had a first potentially avoidable hospitalization from January 1995 through March 2019 (n = 725,939) were defined as cases, and 1:1 age- and sex-matched general population controls (n = 725,939). Preadmission morbidity and healthcare utilization were assessed based on a complete hospital diagnosis history within 10 years prior, and all medication use and healthcare contacts 1 year prior. Using log-binomial regression, we calculated adjusted prevalence ratios (PR) with 95% confidence intervals (CI). RESULTS: Included cases and controls had a median age of 78 years and 59% were female. The burden of preadmission morbidity was higher among cases than controls. The strongest associations were observed for preadmission chronic lung disease (PR 3.8, CI 3.7-3.8), alcohol-related disease (PR 3.1, CI 3.0-3.2), chronic kidney disease (PR 2.4, CI 2.4-2.5), psychiatric disease (PR 2.2, CI 2.2-2.3), heart failure (PR 2.2, CI 2.2-2.3), and previous hospital contacts with infections (PR 2.2, CI 2.2-2.3). A high and accelerating number of healthcare contacts was observed during the months preceding the potentially avoidable hospitalization (having over 5 GP contacts 1 month prior, PR 3.0, CI 3.0-3.0). CONCLUSION: A high number of healthcare contacts and preadmission morbidity and medication use, especially chronic lung, heart, and kidney disease, alcohol-related or psychiatric disease including dementia, and previous infections are strongly associated with potentially avoidable hospitalizations.

Defining measures of kidney function in observational studies using routine health care data: methodological and reporting considerations.

The availability of electronic health records and access to a large number of routine measurements of serum creatinine and urinary albumin enhance the possibilities for epidemiologic research in kidney disease. However, the frequency of health care use and laboratory testing is determined by health status and indication, imposing certain challenges when identifying patients with kidney injury or disease, when using markers of kidney function as covariates, or when evaluating kidney outcomes. Depending on the specific research question, this may influence the interpretation, generalizability, and/or validity of study results. This review illustrates the heterogeneity of working definitions of kidney disease in the scientific literature and discusses advantages and limitations of the most commonly used approaches using 3 examples. We summarize ways to identify and overcome possible biases and conclude by proposing a framework for reporting definitions of exposures and outcomes in studies of kidney disease using routinely collected health care data.

Defining Baseline Creatinine for Identification of AKI in Population-Based Laboratory Databases: A Danish Nationwide Cohort Study.

Background: The baseline creatinine level is central in the Kidney Disease Improving Global Outcomes (KDIGO) criteria of AKI, but baseline creatinine is often inconsistently defined or unavailable in AKI research. We examined the rate, characteristics, and 30-day mortality of AKI in five AKI cohorts created using different definitions of baseline creatinine. Methods: This nationwide cohort study included all individuals aged ≥18 years in Denmark with a creatinine measurement in 2017. Applying the KDIGO criteria, we created four AKI cohorts using four different baseline definitions (most recent, mean, or median value of outpatient creatinine 365-368 days before, or median value 90-98 days before, if available, otherwise median value 365-391 days before) and one AKI cohort not using a baseline value. AKI rate and the distribution of age, sex, baseline creatinine, and comorbidity were described for each AKI cohort, and the 30-day all-cause mortality was estimated using the Kaplan-Meier method. Results: The study included 2,095,850 adults with at least one creatinine measurement in 2017. The four different baseline definitions identified between 61,189 and 62,597 AKI episodes. The AKI rate in these four cohorts was 13-14 per 1000 person-years, and 30-day all-cause mortality was 17%-18%. The cohort created without using a baseline creatinine included 37,659 AKI episodes, corresponding to an AKI rate of 8.2 per 1000 person-years and a 30-day mortality of 23%. All five cohorts were similar regarding age, sex, and comorbidity. Conclusions: In a population-based setting with available outpatient baseline creatinine, different baseline creatinine definitions revealed comparable AKI cohorts, whereas the lack of a baseline creatinine when defining AKI led to a smaller AKI cohort with a higher mortality. These findings underscore the importance of availability and consistent use of an outpatient baseline creatinine, particulary in studies of community-acquired AKI.

Kidney disease and risk of dementia: a Danish nationwide cohort study.

OBJECTIVES: It is unclear whether kidney disease is a risk factor for developing dementia. We examined the association between kidney disease and risk of future dementia. DESIGN AND SETTING: Nationwide historical registry-based cohort study in Denmark based on data from 1 January 1995 until 31 December 2016. PARTICIPANTS: All patients diagnosed with kidney disease and matched general population cohort without kidney disease (matched 1:5 on age, sex and year of kidney disease diagnosis). PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause dementia and its subtypes: Alzheimer's disease, vascular dementia and other specified or unspecified dementia. We computed 5-year cumulative incidences (risk) and hazard ratios (HRs) for outcomes using Cox regression analyses. RESULTS: The study cohort comprised 82 690 patients with kidney disease and 413 405 individuals from the general population. Five-year and ten-year mortality rates were twice as high in patients with kidney disease compared with the general population. The 5-year risk for all-cause dementia was 2.90% (95% confidence interval: 2.78% to 3.08%) in patients with kidney disease and 2.98% (2.92% to 3.04%) in the general population. Compared with the general population, the adjusted HRs for all-cause dementia in patients with kidney disease were 1.06 (1.00 to 1.12) for the 5-year follow-up and 1.08 (1.03 to 1.12) for the entire study period. Risk estimates for dementia subtypes differed substantially and were lower for Alzheimer's disease and higher for vascular dementia. CONCLUSIONS: Patients diagnosed with kidney disease have a modestly increased rate of dementia, mainly driven by vascular dementia. Moreover, patients with kidney disease may be underdiagnosed with dementia due to high mortality and other comorbidities of higher priority.

Risk factors of hospitalisation for thrombosis in adults with primary immune thrombocytopenia, including disease-specific treatments: a French nationwide cohort study.

We aimed to assess the risk factors of venous thrombosis (VT) and arterial thrombosis (AT) in adults with primary immune thrombocytopenia (ITP), particularly in relation to treatments. The population comprised all incident primary ITP adults in France between 2009 and 2017 (FAITH cohort; NCT03429660) built in the national health database. Outcomes were the first hospitalisation for VT and AT. Multivariable Cox regression models included baseline risk factors, time-varying exposure to ITP drugs, splenectomy and to cardiovascular drugs. The cohort included 10 039 patients. A higher risk of hospitalisation for VT was observed with older age, history of VT, history of cancer, splenectomy [hazard ratio (HR) 3·23, 95% confidence interval (CI) 2·26-4·61], exposure to corticosteroids (HR 3·55, 95% CI 2·74-4·58), thrombopoietin-receptor agonists (TPO-RAs; HR 2·28, 95% CI 1·59-3·26) and intravenous immunoglobulin (IVIg; HR 2·10, 95% CI 1·43-3·06). A higher risk of hospitalisation for AT was observed with older age, male sex, a history of cardiovascular disease, splenectomy (HR 1·50, 95% CI 1·12-2·03), exposure to IVIg (HR 1·85, 95% CI 1·36-2·52) and TPO-RAs (HR 1·64, 95% CI 1·26-2·13). Rituximab was not associated with an increased risk. These findings help to estimate the risk of thrombosis in adult patients with ITP and to select treatment.

Lessons Learned Using Real-World Data to Emulate Randomized Trials: A Case Study of Treatment Effectiveness for Newly Diagnosed Immune Thrombocytopenia.

Regulatory agencies are increasingly considering real-world evidence (RWE) to support label expansions of approved medicines. We conducted a comparative effectiveness study to emulate a proposed randomized trial of romiplostim vs. standard-of-care (SOC) therapy among patients with recently diagnosed (≤12 months) immune thrombocytopenia (ITP), that could support expansion of the romiplostim label. We discuss challenges that we encountered and solutions that were developed to address those challenges. Study size was a primary concern, particularly for romiplostim initiators, given the rarity of ITP and the stringent trial eligibility criteria. For this reason, we leveraged multiple data sources (Nordic Country Patient Registry for Romiplostim; chart review study of romiplostim initiators in Europe; Flatiron Health EMR linked with MarketScan claims). Additionally, unlike the strictly controlled clinical trial setting, platelet counts were not measured at regular intervals in the observational data sources, and therefore the end point of durable platelet response often used in trials could not be reliably measured. Instead, the median platelet count was chosen as the primary end point. Ultimately, while we observed a slightly higher median platelet count in the romiplostim group vs. SOC, precision was limited because of small study size (median difference was 11 × 109 /L (95% CI: -59, 81)). We underscore the importance of conducting comprehensive feasibility assessments to identify fit-for-purpose data sources with sufficient sample size, data elements, and follow-up. Beyond technical challenges, we also discuss approaches to increase the credibility of RWE, including systematic incorporation of clinical expertise into study design decisions, and separation between decision makers and the data.

The association between initial opioid type and long-term opioid use after hip fracture surgery in elderly opioid-naïve patients.

Objectives Long-term opioid use after hip fracture surgery has been demonstrated in previously opioid-naïve elderly patients. It is unknown if the opioid type redeemed after hip surgery is associated with long-term opioid use. The aim of this study was to examine the association between the opioid type redeemed within the first three months after hip fracture surgery and opioid use 3-12 months after the surgery. Methods A nationwide population-based cohort study was conducted using data from Danish health registries (2005-2015). Previously opioid-naïve patients registered in the Danish Multidisciplinary Hip Fracture Registry, aged ≥65 years, who redeemed ≥1 opioid prescription within three months after the surgery, were included. Long-term opioid use was defined as ≥1 redeemed prescription within each of three three-month periods within the year after hip fracture surgery. The proportion with long-term opioid use after surgery, conditioned on nine-month survival, was calculated according to opioid types within three months after surgery. Adjusted odds ratios (aOR) for different opioid types were computed by logistic regression analyses with 95% confidence intervals (CI) using morphine as reference. Subgroup analyses were performed according to age, comorbidity and calendar time before and after 2010. Results The study included 26,790 elderly, opioid-naïve patients with opioid use within three months after hip fracture surgery. Of these patients, 21% died within nine months after the surgery. Among the 21,255 patients alive nine months after surgery, 15% became long-term opioid users. Certain opioid types used within the first three months after surgery were associated with long-term opioid use compared to morphine (9%), including oxycodone (14%, aOR; 1.76, 95% CI 1.52-2.03), fentanyl (29%, aOR; 4.37, 95% CI 3.12-6.12), codeine (13%, aOR; 1.55, 95% CI 1.14-2.09), tramadol (13%, aOR; 1.56, 95% CI 1.35-1.80), buprenorphine (33%, aOR; 5.37, 95% CI 4.14-6.94), and >1 opioid type (27%, aOR; 3.83, 95% CI 3.31-4.44). The proportion of long-term opioid users decreased from 18% before 2010 to 13% after 2010. Conclusions The findings suggest that use of certain opioid types after hip fracture surgery is more associated with long-term opioid use than morphine and the proportion initiating long-term opioid use decreased after 2010. The findings suggest that some elderly, opioid-naïve patients appear to be presented with untreated pain conditions when seen in the hospital for a hip fracture surgery. Decisions regarding the opioid type prescribed after hospitalization for hip fracture surgery may be linked to different indication for pain treatment, emphasizing the likelihood of careful and conscientious opioid prescribing behavior.

Renin-angiotensin system blockers and 1-year mortality in patients with post-operative acute kidney injury.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin-receptor blocker (ARB) users may be associated with increased mortality in patients with post-operative acute kidney injury (AKI), but data are limited. We studied whether users of ACE-I/ARBs with AKI after colorectal cancer surgery (CRC) were associated with increased 1-year mortality after AKI. METHODS: This population-based cohort study in Northern Denmark included patients with AKI within 7 days after CRC surgery during 2005-2014. From reimbursed prescriptions, patients were classified as ACE-I/ARB current, former, or non-users. We computed the cumulative 30-day and 1-year mortality after AKI with 95% confidence intervals (95% CI) using the Kaplan-Meier method (1-survival function). Hazard ratios (HRs) comparing mortality in current and former users with non-users were computed by Cox proportional hazards regression analyses, controlling for potential confounders. RESULTS: We identified 10 713 CRC surgery patients. A total of 2000 patients had AKI and were included. Thirty-day mortality was 16.5% (95% CI 13.7-19.8), 16.2% (95% CI 11.3-22.8), and 13.4% (95% CI 11.6-15.4) for current, former, and non-users. Adjusted HR was 1.26 (95% CI 0.96-1.65) and 1.19 (95% CI 0.78-1.82) for current and former users compared with non-users. One-year mortality rates were 26.4% (95% CI 22.9-30.4), 29.8% (95% CI 23.2-37.8), and 24.7% (95% CI 22.4-27.2) in current, former, and non-users. Compared with non-users, the adjusted 1-year HR for death in current and former users were 1.29 (95% CI 0.96-1.73) and 1.11 (95% CI 0.91-1.35). CONCLUSION: Based on our findings, current users of ACE-I/ARB may possibly have a small increase in mortality rate in the year after post-operative AKI, although the degree of certainty is low.

Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has triggered several hypotheses regarding use of specific medicines and risk of infection as well as prognosis. Under these unique circumstances, rapid answers require quick engagement in data collection and analyses; however, appropriate design and conduct of pharmacoepidemiologic studies are needed to generate valid and reliable evidence. In this paper, endorsed by the International Society for Pharmacoepidemiology, we provide methodological considerations for the conduct of pharmacoepidemiological studies in relation to the pandemic across eight domains: (1) timeliness of evidence, including the need to prioritise some questions over others in the acute phase of the pandemic; (2) the need to align observational and interventional research on efficacy; (3) the specific challenges related to "real-time epidemiology" during an ongoing pandemic; (4) what design to use to answer a specific question; (5) considerations on the definition of exposures; (6) what covariates to collect; (7) considerations on the definition of outcomes; and (8) the need for transparent reporting.

The Validity of Registered Synchronous Peritoneal Metastases from Colorectal Cancer in the Danish Medical Registries.

INTRODUCTION: Treatment options for peritoneal metastases (PM) from colorectal cancer (CRC) have increased, their efficiency should be monitored. For this purpose, register-based data on PM can be used, if valid. PURPOSE: We aimed to evaluate the completeness and positive predictive value (PPV) of synchronous peritoneal metastases (S-PM) registered among CRC patients in the Danish National Patient Register (DNPR) and/or the Danish National Pathology Register (the DNPatR) using the Danish Colorectal Cancer Group database (DCCG) as a reference. PATIENTS AND METHODS: We identified Danish patients with newly diagnosed primary CRC in the DCCG during 2014-2015. S-PM were routinely registered in the DCCG. We excluded patients with non-CRC cancers and identified S-PM using all three registries. We estimated the completeness and the PPV of registered S-PM in the DNPR, the DNPatR and the DNPR and/or the DNPatR (DNPR/DNPatR) in combination using the DCCG as the reference. We stratified by age, gender, WHO performance status, tumour location and distant metastases to liver and/or lungs. RESULTS: We identified 9142 patients with CRC in DCCG. In DCCG, 366 patients were registered with S-PM, among whom 213 in DCCG only, whereas 153 in DCCG and in at least one of DNPR and/or DNPatR. In DNPR/DNPatR, S-PM was registered with a completeness of 42% [95% CI: 37-47] and a PPV of 60% [95% CI: 54-66]. In the DNPR only, the completeness was 32% [95% CI: 27-37] and the PPV 57% [95% CI: 50-64]. The completeness in the DNPatR was 19% [95% CI: 15-23] and the PPV was 76% [95% CI: 68-85]. In the DNPR/DNPatR patients aged <60 years (57% [95% CI: 46-69]), patients with WHO performance status 0 (46% [95% CI: 37-54]) and patients with no distant metastases (58% [95% CI: 50-65]) were registered with a higher completeness. CONCLUSION: Our algorithm demonstrates that the DNPR/DNPatR captures less than half of CRC patients with S-PM. Potential candidates for curative treatment options are registered with a higher completeness. Clinicians should be encouraged to register the presence of S-PM to increase the validity of register-based S-PM data.

Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study.

BACKGROUND: Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. METHODS: This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. RESULTS: Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2-3.2) in metformin users and 1.6 (1.0-2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. CONCLUSION: In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

One-year mortality among non-surgical patients with hematological malignancies admitted to the intensive care unit: a Danish nationwide population-based cohort study.

PURPOSE: Contemporary data on mortality of hematological patients admitted to the intensive care unit (ICU) are missing. In a Danish nationwide set-up, we assessed 30-day and 1-year mortality in this population including impact of age and comorbidity, with non-hematological patients as reference. METHODS: This population-based cohort study included all non-surgical patients > 15 years of age admitted to an ICU in Denmark between 2010 and 2015. Data on hematological malignancies were obtained from the Danish Hematological Database, and information on the Charlson Comorbidity Index was obtained from the Danish National Patient Registry. Thirty-day and 1-year mortality was estimated using the Kaplan-Meier method. We used Cox proportional hazards regression to estimate hazard ratios. RESULTS: We included 2122 ICU patients with a hematological malignancy and 88,951 non-hematological ICU patients. The 30-day mortality was 44% (95% confidence interval: 42-47%) among hematological patients and 27% (27-27%) among non-hematological patients. Similarly, 1-year mortality was 66% (64-68%) and 37% (37-37%), respectively. The corresponding hazard ratio with adjustment for age, sex, and comorbidity was 1.62 (1.54-1.71). Excess mortality was observed in all subgroups of age or of comorbidity. For example, the 1-year mortality for patients with Charlson Comorbidity Index Score > 3: 70% (66-74%) among hematological patients and 62% (61-63%) among non-hematological patients. CONCLUSION: ICU patients with hematological malignancy had higher mortality than other ICU patients. However, one third of critically ill patients with a hematological malignancy is alive 1 year after ICU admission.

Intubation rate, duration of noninvasive ventilation and mortality after noninvasive neurally adjusted ventilatory assist (NIV-NAVA).

BACKGROUND: Asynchrony is a common problem in patients treated with noninvasive ventilation (NIV). Neurally adjusted ventilatory assist (NAVA) has shown to improve patient-ventilator interaction. However, it is unknown whether NIV-NAVA improves outcomes compared to noninvasive pressure support (NIV-PS). METHODS: This observational cohort study included patients 18 years or older receiving noninvasive ventilation using an oro-nasal face mask for more than 2 hours in a Danish ICU. The study included a NIV-NAVA cohort (year 2013-2015) and two comparison cohorts: (a) a historical NIV-PS cohort (year 2011-2012) before the implementation of NIV-NAVA at the ICU in 2013, and (b) a concurrent NIV-PS cohort (year 2013-2015). Outcomes of NIV-NAVA (intubation rate, duration of NIV and 90-day mortality) were assessed and compared using multivariable linear and logistic regression adjusted for relevant confounders. RESULTS: The study included 427 patients (91 in the NIV-NAVA, 134 in the historic NIV-PS and 202 in the concurrent NIV-PS cohort). Patients treated with NIV-NAVA did not have improved outcome after adjustment for measured confounders. Actually, there were statistically imprecise higher odds for intubation in NIV-NAVA patients compared with both the historical [OR 1.48, CI (0.74-2.97)] and the concurrent NIV-PS cohort [OR 1.67, CI (0.87-3.19)]. NIV-NAVA might also have a longer length of NIV [63%, CI (19%-125%)] and [139%, CI (80%-213%)], and might have a higher 90-day mortality [OR 1.24, CI (0.69-2.25)] and [OR 1.39, CI (0.81-2.39)]. Residual confounding cannot be excluded. CONCLUSION: This present study found no improved clinical outcomes in patients treated with NIV-NAVA compared to NIV-PS.