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.

Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL).

PURPOSE: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety. METHODS: In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition. RESULTS: Six hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0-24] and 14 [0-24], number of days alive and discharged from the ICU through day 28 were 15 [0-22] and 10 [0-22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group. CONCLUSION: Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified.

Regional variation in incidence and prognosis of acute kidney injury.

BACKGROUND: Examining regional variation in acute kidney injury (AKI) and associated outcomes may reveal inequalities and possibilities for optimization of the quality of care. Using the Danish medical databases, we examined regional variation in the incidence, follow-up, and prognosis of AKI in Denmark. METHODS: Patients with one or more AKI episodes in 2017 were identified using population-based creatinine measurements covering all Danish residents. Crude and sex-and-age-standardized incidence rates of AKI were estimated using census statistics for each municipality. Adjusted hazard ratios (aHR) of chronic kidney disease (CKD), all-cause death, biochemical follow-up, and outpatient contact with a nephrology department after AKI were estimated across geographical regions and categories of municipalities, accounting for differences in demographics, comorbidities, medication use, lifestyle and social factors, and baseline kidney function. RESULTS: We identified 63 382 AKI episodes in 58 356 adults in 2017. The regional standardized AKI incidence rates ranged from 12.9 to 14.9 per 1 000 person-years. Compared with the Capital Region of Denmark, the aHRs across regions ranged from 1.04 to 1.25 for CKD, from 0.97 to 1.04 for all-cause death, from 1.09 to 1.15 for biochemical follow-up, and from 1.08 to 1.49 for outpatient contact with a nephrology department after AKI. Similar variations were found across municipality categories. CONCLUSIONS: Within the uniform Danish healthcare system, we found modest regional variation in AKI incidence. The mortality after AKI was similar; however, CKD, biochemical follow-up, and nephrology follow-up after AKI varied across regions and municipality categories.

Kidney function before and after acute kidney injury: a nationwide population-based cohort study.

Background: Acute kidney injury (AKI) is a common and serious condition defined by a rapid decline in kidney function. Data on changes in long-term kidney function following AKI are sparse and conflicting. Therefore, we examined the changes in estimated glomerular filtration rate (eGFR) from before to after AKI in a nationwide population-based setting. Methods: Using Danish laboratory databases, we identified individuals with first-time AKI defined by an acute increase in plasma creatinine (pCr) during 2010 to 2017. Individuals with three or more outpatient pCr measurements before and after AKI were included and cohorts were stratified by baseline eGFR (≥/<60 mL/min/1.73 m2). Linear regression models were used to estimate and compare individual eGFR slopes and eGFR levels before and after AKI. Results: Among individuals with a baseline eGFR ≥60 mL/min/1.73 m2 (n = 64 805), first-time AKI was associated with a median difference in eGFR level of -5.6 mL/min/1.73 m2 [interquartile range (IQR) -16.1 to 1.8] and a median difference in eGFR slope of -0.4 mL/min/1.73 m2/year (IQR -5.5 to 4.4). Correspondingly, among individuals with a baseline eGFR <60 mL/min/1.73 m2 (n = 33 267), first-time AKI was associated with a median difference in eGFR level of -2.2 mL/min/1.73 m2 (IQR -9.2 to 4.3) and a median difference in eGFR slope of 1.5 mL/min/1.73 m2/year (IQR -2.9 to 6.5). Conclusion: Among individuals with first-time AKI surviving to have repeated outpatient pCr measurements, AKI was associated with changes in eGFR level and eGFR slope for which the magnitude and direction depended on baseline eGFR.

Perioperative Doppler measurements of renal perfusion are associated with acute kidney injury in patients undergoing cardiac surgery.

Acute kidney injury (AKI) is a frequent and severe complication in cardiac surgery. Normal renal function is dependent on adequate renal perfusion, which may be altered in the perioperative period. Renal perfusion can be assessed with Doppler measurement. We aimed to determine the association between Doppler measurements of renal perfusion and the development of AKI. This was a prospective, observational study of 100 patients with ≥ one risk factor for postoperative AKI undergoing open-heart surgery. Doppler ultrasound examinations were performed before surgery and on the first and fourth postoperative day. AKI was defined according to the KDIGO criteria and subdivided into mild (KDIGO stage 1) and severe AKI (KDIGO stage 2 + 3). Thirty-three patients developed AKI, 25 developed mild and eight developed severe AKI. Abnormal renal venous flow pattern on the first postoperative day was significantly associated with the development of severe AKI (OR 8.54 (95% CI 1.01; 72.2), P = 0.046), as were portal pulsatility fraction (OR 1.07 (95% CI 1.02; 1.13), P = 0.005). Point-of-care Doppler ultrasound measurements of renal perfusion are associated with the development of AKI after cardiac surgery. Renal and portal Doppler ultrasonography can be used to identify patients at high risk or very low risk of AKI after cardiac surgery.

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.

Acute kidney injury and 1-year mortality after colorectal cancer surgery: a population-based cohort study.

OBJECTIVES: Acute kidney injury (AKI) is a frequent postoperative complication, but the mortality impact within different postoperative time frames and severities of AKI are poorly understood. We examined the occurrence of postoperative AKI among colorectal cancer (CRC) surgery patients and the impact of AKI on mortality during 1 year after surgery. DESIGN: Observational cohort study. We defined the exposure, AKI, as a 50% increase in plasma creatinine or initiation of renal replacement therapy within 7 days after surgery or an absolute increase in creatinine of 26 µmol/L within 48 hours. SETTING: Population-based Danish medical databases. PARTICIPANTS: A total of 6580 patients undergoing CRC surgery in Northern Denmark during 2005-2011 were included from the Danish Colorectal Cancer Group database. OUTCOMES MEASURE: Occurrence of AKI and 8-30, 31-90 and 91-365 days mortality in patient with or without AKI. RESULTS: AKI occurred in 1337 patients (20.3%) of the 6580 patients who underwent CRC surgery. Among patients with AKI, 8-30, 31-90 and 91-365 days mortality rates were 10.1% (95% CI 8.6% to 11.9%), 7.8% (95% CI 6.4% to 9.5%) and 12.0% (95% CI 10.3% to 14.2%), respectively. Compared with patients without AKI, AKI was associated with increased 8-30 days mortality (adjusted HR (aHR)=4.01,95% CI 3.11 to 5.17) and 31-90 days mortality (aHR 2.08,95% CI 1.60 to 2.69), while 91-365 days aHR was 1.12 (95% CI 0.89 to 1.41). We observed no major differences in stratified analyses. CONCLUSIONS: AKI after surgery for CRC is a frequent postoperative complication associated with a substantially increased 90-day mortality. AKI should be considered a potential target for reducing 90-day mortality.

Liver disease and mortality among patients with hip fracture: a population-based cohort study.

PURPOSE: The aim of this study was to examine the prognostic impact of liver disease on mortality following hip fracture (HF). PATIENTS AND METHODS: This nationwide cohort study, based on prospectively collected data retrieved from Danish registries, included all patients diagnosed with incident HF in Denmark during 1996-2013. Patients were classified based on the coexisting liver disease at the time of HF, ie, no liver disease, noncirrhotic liver disease, and liver cirrhosis. We computed 30-day and 31-365-day mortality risks. To compare patients with and without liver disease, we computed mortality adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using Cox regression controlled for potential confounders. RESULTS: Among 152,180 HF patients, 2,552 (1.7%) patients had noncirrhotic liver disease and 1,866 (1.2%) patients had liver cirrhosis. Thirty-day mortality was 9.4% among patients with noncirrhotic liver disease, 12.6% among patients with liver cirrhosis patients, and 9.7% among patients without liver disease. Compared to patients without liver disease, crude and adjusted HRs within 30 days following HF were, respectively, 0.96 (95% CI: 0.85-1.10) and 1.24 (95% CI: 1.09-1.41) for patients with noncirrhotic liver disease and 1.30 (95% CI: 1.14-1.48) and 2.25 (95% CI: 1.96-2.59) for those with liver cirrhosis. Among patients who survived 30 days post-HF, the 31-365-day mortality was 18.5% among patients with noncirrhotic liver disease, 26.4% among patients with liver cirrhosis, and 19.4% among patients without liver disease. Corresponding crude and adjusted HRs were, respectively, 0.95 (95% CI: 0.86-1.04) and 1.08 (95% CI: 0.99-1.20) for patients with noncirrhotic liver disease and 1.40 (95% CI: 1.27-1.54) and 1.91 (95% CI: 1.72-2.12) for those with liver cirrhosis. CONCLUSION: Liver disease patients, especially those with liver cirrhosis, had increased 30-day mortality and 31-365-day mortality following HF, compared to patients without liver disease.

Timing of renal replacement therapy and long-term risk of chronic kidney disease and death in intensive care patients with acute kidney injury.

BACKGROUND: The optimal time to initiate renal replacement therapy (RRT) in intensive care unit (ICU) patients with acute kidney injury (AKI) is unclear. We examined the impact of early RRT on long-term mortality, risk of chronic kidney disease (CKD), and end-stage renal disease (ESRD). METHODS: This cohort study included all adult patients treated with continuous RRT in the ICU at Aarhus University Hospital, Skejby, Denmark (2005-2015). Data were obtained from a clinical information system and population-based registries. Early treatment was defined as RRT initiation at AKI stage 2 or below, and late treatment was defined as RRT initiation at AKI stage 3. Inverse probability of treatment (IPT) weights were computed from propensity scores. The IPT-weighted cumulative risk of CKD (estimated glomerular filtration rate < 60 ml/minute/1.73 m2), ESRD, and mortality was estimated and compared using IPT-weighted Cox regression. RESULTS: The mortality, CKD, and ESRD analyses included 1213, 303, and 617 patients, respectively. The 90-day mortality in the early RRT group was 53.6% compared with 46.0% in the late RRT group (HR 1.24, 95% CI 1.03-1.48). The 90-day to 5-year mortality was 37.7% and 41.5% in the early and late RRT groups, respectively (HR 0.95, 95% CI 0.70-1.29). The 5-year risk of CKD was 35.9% in the early RRT group and 44.9% in the late RRT group (HR 0.74, 95% CI 0.46-1.18). The 5-year risk of ESRD was 13.3% in the early RRT group and 16.7% in the late RRT group (HR 0.79, 95% CI 0.47-1.32). CONCLUSIONS: Early initiation was associated with increased 90-day mortality. In patients surviving to day 90, early initiation was not associated with a major impact on long-term mortality or risk of CKD and ESRD. Despite potential residual confounding due to the observational design, our findings do not support that early RRT initiation is superior to late initiation.

Control of confounding in the analysis phase - an overview for clinicians.

In observational studies, control of confounding can be done in the design and analysis phases. Using examples from large health care database studies, this article provides the clinicians with an overview of standard methods in the analysis phase, such as stratification, standardization, multivariable regression analysis and propensity score (PS) methods, together with the more advanced high-dimensional propensity score (HD-PS) method. We describe the progression from simple stratification confined to the inclusion of a few potential confounders to complex modeling procedures such as the HD-PS approach by which hundreds of potential confounders are extracted from large health care databases. Stratification and standardization assist in the understanding of the data at a detailed level, while accounting for potential confounders. Incorporating several potential confounders in the analysis typically implies the choice between multivariable analysis and PS methods. Although PS methods have gained remarkable popularity in recent years, there is an ongoing discussion on the advantages and disadvantages of PS methods as compared to those of multivariable analysis. Furthermore, the HD-PS method, despite its generous inclusion of potential confounders, is also associated with potential pitfalls. All methods are dependent on the assumption of no unknown, unmeasured and residual confounding and suffer from the difficulty of identifying true confounders. Even in large health care databases, insufficient or poor data may contribute to these challenges. The trend in data collection is to compile more fine-grained data on lifestyle and severity of diseases, based on self-reporting and modern technologies. This will surely improve our ability to incorporate relevant confounders or their proxies. However, despite a remarkable development of methods that account for confounding and new data opportunities, confounding will remain a serious issue. Considering the advantages and disadvantages of different methods, we emphasize the importance of the clinical input and of the interplay between clinicians and analysts to ensure a proper analysis.

Acute kidney injury treated with renal replacement therapy and 5-year mortality after myocardial infarction-related cardiogenic shock: a nationwide population-based cohort study.

BACKGROUND: Myocardial infarction-related cardiogenic shock is frequently complicated by acute kidney injury. We examined the influence of acute kidney injury treated with renal replacement therapy (AKI-RRT) on risk of chronic dialysis and mortality, and assessed the role of comorbidity in patients with cardiogenic shock. METHODS: In this Danish cohort study conducted during 2005-2012, we used population-based medical registries to identify patients diagnosed with first-time myocardial infarction-related cardiogenic shock and assessed their AKI-RRT status. We computed the in-hospital mortality risk and adjusted relative risk. For hospital survivors, we computed 5-year cumulative risk of chronic dialysis accounting for competing risk of death. Mortality after discharge was computed with use of Kaplan-Meier methods. We computed 5-year hazard ratios for chronic dialysis and death after discharge, comparing AKI-RRT with non-AKI-RRT patients using a propensity score-adjusted Cox regression model. RESULTS: We identified 5079 patients with cardiogenic shock, among whom 13% had AKI-RRT. The in-hospital mortality was 62% for AKI-RRT patients, and 36% for non-AKI-RRT patients. AKI-RRT remained associated with increased in-hospital mortality after adjustment for confounders (relative risk=1.70, 95% confidence interval (CI): 1.59-1.81). Among the 3059 hospital survivors, the 5-year risk of chronic dialysis was 11% (95% CI: 8-16%) for AKI-RRT patients, and 1% (95% CI: 0.5-1%) for non-AKI-RRT patients (adjusted hazard ratio: 15.9 (95% CI: 8.7-29.3). The 5-year mortality was 43% (95% CI: 37-53%) for AKI-RRT patients compared with 29% (95% CI: 29-31%) for non-AKI-RRT patients. The adjusted 5-year hazard ratio for death was 1.55 (95% CI: 1.22-1.96) for AKI-RRT patients compared with non-AKI-RRT patients. In patients with comorbidity, absolute mortality increased while relative impact of AKI-RRT on mortality decreased. CONCLUSION: AKI-RRT following myocardial infarction-related cardiogenic shock predicted elevated short-term mortality and long-term risk of chronic dialysis and mortality. The impact of AKI-RRT declined with increasing comorbidity suggesting that intensive treatment of AKI-RRT should be accompanied with optimized treatment of comorbidity when possible.

Hospital use among patients with lung cancer complicated by bone metastases and skeletal- related events: a population-based cohort study in Denmark.

OBJECTIVE: Skeletal-related events (SREs) among patients with bone metastases from lung cancer may be associated with considerable use of health care resources. We analyzed in- and outpatient hospital contacts in relation to SREs among all Danish lung cancer patients with bone metastases. METHODS: For this cohort study, we used the Danish Cancer Registry and the Danish National Registry of Patients to identify all persons diagnosed with first-time lung cancer and bone metastases from 2003 through 2009 in Denmark. We followed these patients until December 31, 2010, for the development of SREs (spinal cord compression; pathological or osteoporotic fracture, surgery to bone; or conventional external radiation therapy). We examined the number of inpatient hospitalizations, inpatient bed-days, hospital outpatient clinic visits, and emergency room visits within three time periods: a pre-SRE period (90-day period prior to the diagnostic period), a SRE diagnostic period (14-day period prior to the SRE), and a post-SRE period (90-day period after the SRE). RESULTS: We identified 1,146 patients with lung cancer, bone metastases, and ≥1 subsequent SRE among 28,443 patients with incident lung cancer. Over 75% of patients with SREs (n=852) had more than one SRE. The number of hospital bed-days was high in the post-SRE period compared to the pre-SRE period, as illustrated by patients with multiple SREs who had 10.7 (95% confidence interval, 10.4-10.9) hospital bed-days per 100 person-days in the pre-SRE period and 28.2 (95% confidence interval, 27.8-28.6) bed-days per 100 person-days in the post-SRE period. CONCLUSION: SREs secondary to bone metastases in lung cancer patients are associated with a substantial number of hospital contacts and hospital bed-days.

Evaluation of an ICD-10 algorithm to detect osteonecrosis of the jaw among cancer patients in the Danish National Registry of Patients.

PURPOSE: This study aimed to validate a predefined algorithm for osteonecrosis of the jaw (ONJ) among cancer patients in the Danish National Registry of Patients and to assess the nature of clinical information recorded in medical charts of ONJ patients. METHODS: We identified potential ONJ cases recorded in 2005-2010 among cancer patients at the hospital Departments of Oral and Maxillofacial Surgery (DOMS) in three Danish regions, using a set of codes from the International Classification of Diseases, 10th revision (ICD-10). We abstracted DOMS charts of the potential cases, had the ONJ status adjudicated by an expert ONJ adjudication committee (ONJAC), and computed positive predictive values. For patients with ONJAC-confirmed ONJ, we abstracted the charts for information on ONJ clinical course. Sensitivity of the algorithm was computed using a separate sample of 101 known ONJ cases accrued in 2005-2011. RESULTS: We identified 212 potential ONJ cases, of which 197 (93%) had charts available for abstraction. Eighty-three potential cases were confirmed by ONJAC, with a positive predictive value of 42% (95% confidence interval [CI] 35%-49%). DOMS charts of these 83 cases contained complete information on ONJ clinical course. Information about antiresorptive treatment was recorded for 84% of the patients. Among the 101 known ONJ cases, 74 had at least one prespecified ICD-10 code recorded in the Danish National Registry of Patients within ±90 days of the ONJ diagnosis (sensitivity 73%; 95%CI [64%-81%]). CONCLUSIONS: The predefined algorithm is not adequate for monitoring ONJ in pharmacovigilance studies. Additional case-finding approaches, coupled with adjudication, are necessary to estimate ONJ incidence accurately.

Positive predictive value of International Classification of Diseases, 10th revision, diagnosis codes for cardiogenic, hypovolemic, and septic shock in the Danish National Patient Registry.

BACKGROUND: Large registries are important data sources in epidemiological studies of shock, if these registries are valid. Therefore, we examined the positive predictive value (PPV) of diagnosis codes for shock, the procedure codes for inotropic/vasopressor therapy among patients with a diagnosis of shock, and the combination of a shock diagnosis and a code for inotropic/vasopressor therapy in the Danish National Patient Registry (DNPR). METHODS: We randomly selected 190 inpatients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis of shock at Aarhus University Hospital from 2005-2012 using the DNPR; 50 patients were diagnosed with cardiogenic shock, 40 patients with hypovolemic shock, and 100 patients with septic shock. We used medical charts as the reference standard and calculated the PPV with 95% confidence intervals (CI) for overall shock and for each type of shock separately. We also examined the PPV for inotropic/vasopressor therapy and the PPV for shock when a concurrent code for inotropic/vasopressor therapy was also registered. RESULTS: The PPV was 86.1% (95% CI: 79.7-91.1) for shock overall, 93.5% (95% CI: 82.1-98.6) for cardiogenic shock, 70.6% (95% CI: 52.5-84.9) for hypovolemic shock, and 69.2% (95% CI: 57.7-79.2) for septic shock. The PPV of use of inotropes/vasopressors among shock patients was 88.9% (95% CI: 79.3-95.1). When both a shock code and a procedure code for inotropic/vasopressor therapy were used, the PPV for shock overall was 93.1% (95% CI: 84.5-97.7). ICD-10 codes for subtypes of shock and simultaneously registered use of inotropes/vasopressors provided PPVs of 96.0% (95% CI: 79.6-99.9) for cardiogenic shock, 69.2% (95% CI: 38.6-90.9) for hypovolemic shock, and 82.4% (95% CI: 65.5-93.2) for septic shock. CONCLUSIONS: Overall, we found a moderately high PPV for shock in the DNPR. The PPV was highest for cardiogenic shock but lower for hypovolemic and septic shock. Combination diagnoses of shock with codes for inotropic/vasopressor therapy further increased the PPV of shock overall, and for cardiogenic and septic shock diagnoses.

Acute Kidney Injury and Long-term Risk of Cardiovascular Events After Cardiac Surgery: A Population-Based Cohort Study.

OBJECTIVE: To examine the impact of postoperative acute kidney injury (AKI) on the long-term risk of myocardial infarction, heart failure, stroke, and all-cause mortality after elective cardiac surgery. The authors investigated whether time of onset of AKI altered the association between AKI and the adverse events. DESIGN: Population-based cohort study in 2006-2011. SETTING: Two university hospitals. PARTICIPANTS: Adult elective cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKI was defined as an increase in baseline creatinine according to the Kidney Disease Improving Global Outcomes criteria. AKI was defined within 30 days of surgery, and also analyzed as early- or late-onset AKI. The authors followed patients from postoperative day 30 until hospitalization with myocardial infarction, heart failure, stroke, or death. Adjustment for confounding factors was done using propensity scores and standardized-mortality-ratio weights. A total of 1,457 (30.7%) of 4,742 patients developed AKI within 30 days of surgery and 470 (9.9%) patients experienced a composite cardiovascular endpoint. Comparing patients with and without postoperative AKI, weighted hazard ratio (HR) and 95% confidence intervals (CI) of 5-year risk of the composite cardiovascular endpoint was 1.41 (95% CI: 1.11-1.80). For each endpoint separately the weighted HR was similarly increased. Ninety-one days to 5-year weighted HR of all-cause mortality was 1.37 (95% CI: 1.05-1.80). The effect of AKI was similar for early- and late-onset AKI. CONCLUSIONS: Early- and late-onset AKI within 30 days of elective cardiac surgery was associated with a similarly increased 5-year risk of myocardial infarction, heart failure, stroke, and increased all-cause mortality.

Positive predictive value of primary inpatient discharge diagnoses of infection among cancer patients in the Danish National Registry of Patients.

PURPOSE: Pharmacovigilance studies of cancer treatment frequently monitor infections. Predictive values of algorithms identifying disease depend on prevalence of the disease in the population under study. We therefore estimated the positive predictive value (PPV) of primary inpatient diagnosis of infection among cancer patients in the Danish National Registry of Patients (DNRP). METHODS: The algorithm to identify infections in the DNPR was based on International Classification of Diseases, 10th revision (ICD-10) codes. A physician blinded to the type of sampled infection reviewed the medical charts and assessed the presence and type of infection. Using the physician global assessment as gold standard, we computed PPVs with and without requiring agreement on infection type. RESULTS: We retrieved 266 of 272 medical charts (98%). Presence of infection was confirmed in 261 patients, resulting in an overall PPV of 98% (95% confidence interval, 96%-99%). When requiring agreement on infection type, overall PPV was 77%. For skin infections, pneumonia, and sepsis, PPVs were 79%, 93% and 84%, respectively. For these infections, we additionally calculated PPVs using evidence-based criteria as the gold standard. PPV was similar for pneumonia, but lower for skin infections and sepsis. CONCLUSIONS: The Danish National Registry of Patients is suitable for monitoring infections requiring hospitalization among cancer patients.

Three-year risk of cardiovascular disease among intensive care patients with acute kidney injury: a population-based cohort study.

INTRODUCTION: Acute kidney injury (AKI) is common among intensive care unit (ICU) patients, but follow-up data on subsequent risk of cardiovascular disease remain sparse. We examined the impact of AKI on three-year risk of first-time heart failure, myocardial infarction (MI), and stroke among ICU patients surviving to hospital discharge, and whether this risk is modified by renal recovery before hospital discharge. METHODS: We used population-based medical registries to identify all adult patients admitted to an ICU in Northern Denmark between 2005 and 2010 who survived to hospital discharge and who had no previous or concurrent diagnosis of heart failure, MI, or stroke. AKI was defined according to the creatinine criteria in the Kidney Disease Improving Global Outcomes classification. We computed the three-year cumulative risk of hospitalization with heart failure, MI, and stroke for patients with and without AKI and the hazard ratios (HRs), using a Cox model adjusted for potential confounders. RESULTS: Among 21,556 ICU patients surviving to hospital discharge, 4,792 (22.2%) had an AKI episode. Three-year cumulative risk of heart failure was 2.2% in patients without AKI, 5.0% for AKI stage 1, and 5.0% for stages 2 to 3. The corresponding adjusted HRs were 1.33 (95% confidence interval (CI), 1.06 to 1.66) for patients with AKI stage 1 and 1.45 (95% CI, 1.14 to 1.84) for AKI stages 2 to 3, compared to patients without AKI. The three-year cumulative MI risk was 1.0% for patients without AKI, 1.8% for patients with AKI stage 1 and 2.3% for patients with AKI stages 2 to 3. The adjusted HR for MI was 1.04 (95% CI, 0.71 to 1.51) for patients with AKI stage 1 and 1.51 (95% CI, 1.05 to 2.18) for patients with AKI stages 2 to 3, compared with patients without AKI. We found no association between AKI and stroke. The increased risk of heart failure and MI persisted in patients with renal recovery before discharge, although it was less pronounced than in patients without renal recovery. CONCLUSIONS: ICU patients surviving any stage of AKI are at increased three-year risk of heart failure, but not stroke. Only AKI stages 2 to 3 are associated with increased MI risk.

Post-operative acute kidney injury and five-year risk of death, myocardial infarction, and stroke among elective cardiac surgical patients: a cohort study.

INTRODUCTION: The prognostic impact of acute kidney injury (AKI) on long-term clinical outcomes remains controversial. We examined the five-year risk of death, myocardial infarction, and stroke after elective cardiac surgery complicated by AKI. METHODS: We conducted a cohort study among adult elective cardiac surgical patients without severe chronic kidney disease and/or previous heart or renal transplant surgery using data from population-based registries. AKI was defined by the Acute Kidney Injury Network (AKIN) criteria as a 50% increase in serum creatinine from baseline level, acute creatinine rise of ≥26.5 µmol/L (0.3 mg/dL) within 48 hours, and/or initiation of renal replacement therapy within five days after surgery. We followed patients from the fifth post-operative day until myocardial infarction, stroke or death within five years. Five-year risk was computed by the cumulative incidence method and compared with hazards ratios (HR) from a Cox proportional hazards regression model adjusting for propensity score. RESULTS: A total of 287 (27.9%) of 1,030 patients developed AKI. Five-year risk of death was 26.5% (95% CI: 21.2 to 32.0) among patients with AKI and 12.1% (95% CI: 10.0 to 14.7) among patients without AKI. The corresponding adjusted HR of death was 1.6 (95% CI: 1.1 to 2.2). Five-year risk of myocardial infarction was 5.0% (95% CI: 2.9 to 8.1) among patients with AKI and 3.3% (95% CI: 2.1 to 4.8) among patients without AKI. Five-year risk of stroke was 5.0% (95% CI: 2.8 to 7.9) among patients with AKI and 4.2% (95% CI: 2.9 to 5.8) among patients without AKI. Adjusted HRs were 1.5 (95% CI: 0.7 to 3.2) of myocardial infarction and 0.9 (95% CI: 0.5 to 1.8) of stroke. CONCLUSIONS: AKI, within five days after elective cardiac surgery, was associated with increased five-year mortality and a statistically insignificant increased risk of myocardial infarction. No association was seen with the risk of stroke.

Hospitalization rate and 30-day mortality among patients with status asthmaticus in Denmark: a 16-year nationwide population-based cohort study.

OBJECTIVE: Current data on hospitalization and prognosis of acute asthma and status asthmaticus are inconclusive. We aim to analyze the rate of first-time hospitalizations for status asthmaticus among patients of all ages, the proportion admitted to intensive care units (ICU), and the 30-day mortality over a 16-year period. METHODS: In this population-based cohort study, we used medical registries to identify all first-time status asthmaticus hospitalizations in Denmark from 1996 through 2011. Data on comorbidities were also obtained. We computed yearly hospitalization rates overall and by gender and age groups, and estimated the proportion requiring ICU admission. We estimated 30-day age- and gender-standardized mortality. We examined potential misclassification from acute exacerbation of chronic obstructive pulmonary disease (COPD) by excluding patients with preexisting or concurrent COPD. RESULTS: Of the 5,001 patients identified with a first-time status asthmaticus hospitalization, 50.5% were male, 40.3% were <15 years old, and 12.4% had comorbidity. The hospitalization rate increased from 48.0 per 1,000,000 person-years (PY) (95% confidence interval [CI]: 45.1-51.1 PY) during 1996-1999 to 70.1 per 1,000,000 PY (95% CI: 66.7-73.7 PY) during 2008-2011. This may be explained by an increased hospitalization rate of children. The standardized 30-day mortality risk declined from 3.3% (95% CI: 2.5%-4.1%) in 1996-1999 to 1.5% (95% CI: 0.9%-2.1%) in 2008-2011. During 2005-2011, 10.1% of status asthmaticus patients were admitted to the ICU. Hospitalization rates and mortality risk decreased by excluding 939 patients also registered with COPD, but overall temporal changes did not change. CONCLUSION: From 1996 to 2011, status asthmaticus hospitalization rate increased but remained below 100 hospitalizations per 1,000,000 PY. Thirty-day mortality risk was halved to less than 2%.