Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke in Patients with Chronic Kidney Disease

The outcomes of recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke among patients with reduced kidney function are uncertain. We conducted a retrospective cohort study between 2002-2013 to describe rt-PA use and the risk of secondary intracranial hemorrhage (ICH) and disability at discharge. In an overlap weighted cohort of rt-PA eligible patients (1,354), the relative risk (RR) of secondary ICH among those who received rt-PA (vs. no rt-PA) was 2.56 (99% confidence interval (CI) 1.77-3.69) in those with an estimated glomerular filtration rate (eGFR) ≥60, and 2.67 (2.17-6.20) in those with an eGFR 30-59 mL/min/1.73m2. Those treated with rt-PA were more likely to be discharged alive and independent compared no rt-PA (RR ≥60: 1.34 (1.17-1.53), 30-59: 1.53 (1.21-1.93) and, \u3c30/chronic dialysis: 2.13 (0.80-5.67)). rt-PA treated patients versus no rt-PA have a higher risk of bleeding but also have a greater chance of leaving hospital alive and independent

First Results on Survival from a Large Phase 3 Clinical Trial of an Autologous Dendritic Cell Vaccine in Newly Diagnosed Glioblastoma

Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.https://deepblue.lib.umich.edu/bitstream/2027.42/144529/1/12967_2018_Article_1552.pd

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Comparing Five Comorbidity Indices to Predict Mortality in Chronic Kidney Disease: A Retrospective Cohort Study

Background: Several different indices summarize patient comorbidity using health care data. An accurate index can be used to describe the risk profile of patients, and as an adjustment factor in analyses. How well these indices perform in persons with chronic kidney disease (CKD) is not well known. Objective: Assess the performance of 5 comorbidity indices at predicting mortality in 3 different patient groups with CKD: incident kidney transplant recipients, maintenance dialysis patients, and individuals with low estimated glomerular filtration rate (eGFR). Design: Population-based retrospective cohort study. Setting: Ontario, Canada, between 2004 and 2014. Patients: Individuals at the time they first received a kidney transplant, received maintenance dialysis, or were confirmed to have an eGFR less than 45 mL/min per 1.73m 2 . Measurements: Five comorbidity indices: Charlson comorbidity index, end-stage renal disease-modified Charlson comorbidity index, Johns Hopkins’ Aggregated Diagnosis Groups score, Elixhauser score, and Wright-Khan index. Our primary outcome was 1-year all-cause mortality. Methods: Comorbidity indices were estimated using information in the prior 2 years. Each group was randomly divided 100 times into derivation and validation samples. Model discrimination was assessed using median c-statistics from logistic regression models, and calibration was evaluated graphically. Results: We identified 4111 kidney transplant recipients, 23 897 individuals receiving maintenance dialysis, and 181 425 individuals with a low eGFR. Within 1 year, 108 (2.6%), 4179 (17.5%), and 17 898 (9.9%) in each group had died, respectively. In the validation sample, model discrimination was inadequate with median c-statistics less than 0.7 for all 5 comorbidity indices for all 3 groups. Calibration was also poor for all models. Limitations: The study used administrative health care data so there is the potential for misclassification. Indices were modeled as continuous scores as opposed to indicators for individual conditions to limit overfitting. Conclusions: Existing comorbidity indices do not accurately predict 1-year mortality in patients with CKD. Current indices could be modified with additional risk factors to improve their performance in CKD, or a new index could be developed for this population

The Three-Year Incidence of Major Hemorrhage among Older Adults Initiating Chronic Dialysis

Background: For those who initiate chronic dialysis, knowing what proportion will experience 3-year outcomes of hemorrhage with hospitalization informs patient prognosis, disease impact, and the planning of trials and programs to prevent events. Objectives: We examined the incidence of hemorrhage and related gastrointestinal endoscopic procedures in incident older dialysis patients and stratified patients by age, era, dialysis modality and whether recently prescribed anti-thrombotic medication. Design: Retrospective cohort study Setting: Ontario, Canada from 1998 to 2008 (n = 11,173) Patients: All older patients (>65 years) who initiated chronic dialysis Measurements: Hospitalization with hemorrhage and its subtypes (upper and lower gastrointestinal, intra-cerebral, subarachnoid) and related-gastrointestinal procedures. Methods: Three-year outcomes of hospitalization with hemorrhage were expressed as cumulative incidence and incidence rate (number of events per 1,000 patient years). Results were stratified by patient age (66 to 74, 75 to 84, ≥ 85), era (1998 to 2001, 2002 to 2005, 2006 to 2008) and dialysis modality. Among those with hemorrhage, we examined prescriptions for anti-thrombotic medications (warfarin, clopidogrel) in the preceding 120 days. Results: The 3-year cumulative incidence of hemorrhage was 14.4% (roughly 1 in 7 patients). By location, the 3-year cumulative incidence was 8.9% lower gastrointestinal, 6.1% upper gastrointestinal, 0.9% intra-cerebral and 0.1% sub arachnoid hemorrhage. The 3-year cumulative incidence of gastrointestinal endoscopic procedures was 14.8%. The cumulative incidence and rate of hemorrhage were not appreciably different across the 3 age strata, by era or by dialysis modality. Among patients with a hemorrhage, 29.5% were prescribed warfarin in the preceding 120 days, and 8.4% clopidogrel. Limitations: Recurrent events were not included. Conclusions: Many older patients who initiate chronic dialysis will be hospitalized with hemorrhage and receive related procedures over the subsequent three years. Despite greater age and co-morbidity over the last decade this incidence has not changed

The three-year incidence of major hemorrhage among older adults initiating chronic dialysis

Abstract Background For those who initiate chronic dialysis, knowing what proportion will experience 3-year outcomes of hemorrhage with hospitalization informs patient prognosis, disease impact, and the planning of trials and programs to prevent events. Objectives We examined the incidence of hemorrhage and related gastrointestinal endoscopic procedures in incident older dialysis patients and stratified patients by age, era, dialysis modality and whether recently prescribed anti-thrombotic medication. Design Retrospective cohort study Setting Ontario, Canada from 1998 to 2008 (n = 11,173) Patients All older patients (>65 years) who initiated chronic dialysis Measurements Hospitalization with hemorrhage and its subtypes (upper and lower gastrointestinal, intra-cerebral, subarachnoid) and related-gastrointestinal procedures. Methods Three-year outcomes of hospitalization with hemorrhage were expressed as cumulative incidence and incidence rate (number of events per 1,000 patient years). Results were stratified by patient age (66 to 74, 75 to 84, ≥ 85), era (1998 to 2001, 2002 to 2005, 2006 to 2008) and dialysis modality. Among those with hemorrhage, we examined prescriptions for anti-thrombotic medications (warfarin, clopidogrel) in the preceding 120 days. Results The 3-year cumulative incidence of hemorrhage was 14.4% (roughly 1 in 7 patients). By location, the 3-year cumulative incidence was 8.9% lower gastrointestinal, 6.1% upper gastrointestinal, 0.9% intra-cerebral and 0.1% sub arachnoid hemorrhage. The 3-year cumulative incidence of gastrointestinal endoscopic procedures was 14.8%. The cumulative incidence and rate of hemorrhage were not appreciably different across the 3 age strata, by era or by dialysis modality. Among patients with a hemorrhage, 29.5% were prescribed warfarin in the preceding 120 days, and 8.4% clopidogrel. Limitations Recurrent events were not included. Conclusions Many older patients who initiate chronic dialysis will be hospitalized with hemorrhage and receive related procedures over the subsequent three years. Despite greater age and co-morbidity over the last decade this incidence has not changed

Using Administrative Health Care Databases to Identify Patients With End-Stage Kidney Disease With No Recorded Contraindication to Receiving a Kidney Transplant

Background: Administrative health care databases can be efficiently analyzed to describe the degree to which patients with end-stage kidney disease (ESKD) have access to kidney transplantation. Measures of access to transplantation are better represented when restricting to only those patients eligible to receive a kidney transplant. The way administrative data can be used to assess kidney transplant eligibility in the absence of clinical data has not been well described. Objective: To demonstrate a method that uses administrative health care databases to identify patients with ESKD who have no recorded contraindication to receiving a kidney transplant. Design and setting: Population-based cohort study using linked administrative health care databases in Ontario, Canada. Patients: Adult patients with ESKD approaching the need for dialysis (predialysis) or receiving maintenance dialysis between January 1, 2013 and March 31, 2015 in Ontario, Canada. Measurements: Recipient of a kidney-only or kidney-pancreas transplant. Methods: We assessed more than 80 baseline characteristics, including demographic information, comorbidities, kidney-specific characteristics, and referral and listing criteria for kidney transplantation. We compared these characteristics between patients who did and did not receive a kidney transplant. Results: We included 23 642 patients with ESKD (11 195 who were predialysis and 12 447 receiving maintenance dialysis). Over a median follow-up of 3.2 years (25th, 75th percentile: 1.3, 5.6), 3215 (13.6%) received a kidney-only or kidney-pancreas transplant. Of the studied characteristics available in administrative databases, >97% of patients with one or more of these characteristics did not receive a kidney transplant during follow-up: ESKD-modified Charlson Comorbidity Index score ≥7 (a higher score represents greater comorbidity), home oxygen use, age above 75 years, dementia, living in a long-term care facility, receiving at least one physician house call in the past year, and a combination of select malignancies (ie, lung, lymphoma, cervical, colorectal, liver, active multiple myeloma, and bladder cancer). Using these combined criteria reduced the total number of patients from 23 642 to 12 539 with no recorded contraindications to transplant (a 47% reduction), while the proportion who received a kidney transplant changed from 13.6% (denominator of 23 642) to 24.9% (denominator of 12 539). Limitations: Administrative databases are unable to capture all the complexities of determining transplant eligibility. Conclusion: We identified several criteria available within administrative health care databases that can be used to identify patients with ESKD who have no recorded contraindications to kidney transplant. These criteria could be applied when reporting measures of access to kidney transplantation that require knowledge of transplant eligibility