Derivation and validation of a computable phenotype for acute decompensated heart failure in hospitalized patients.

BACKGROUND: With higher adoption of electronic health records at health-care centers, electronic search algorithms (computable phenotype) for identifying acute decompensated heart failure (ADHF) among hospitalized patients can be an invaluable tool to enhance data abstraction accuracy and efficacy in order to improve clinical research accrual and patient centered outcomes. We aimed to derive and validate a computable phenotype for ADHF in hospitalized patients. METHODS: We screened 256, 443 eligible (age > 18 years and with prior research authorization) individuals who were admitted to Mayo Clinic Hospital in Rochester, MN, from January 1, 2006, through December 31, 2014. Using a randomly selected derivation cohort of 938 patients, several iterations of a free-text electronic search were developed and refined. The computable phenotype was subsequently validated in an independent cohort 100 patients. The sensitivity and specificity of the computable phenotype were compared to the gold standard (expert review of charts) and International Classification of Diseases-9 (ICD-9) codes for Acute Heart Failure. RESULTS: In the derivation cohort, the computable phenotype achieved a sensitivity of 97.5%, and specificity of 100%, whereas ICD-9 codes for Acute Heart Failure achieved a sensitivity of 47.5% and specificity of 96.7%. When all Heart Failure codes (ICD-9) were used, sensitivity and specificity were 97.5 and 86.6%, respectively. In the validation cohort, the sensitivity and specificity of the computable phenotype were 100 and 98.5%. The sensitivity and specificity for the ICD-9 codes (Acute Heart Failure) were 42 and 98.5%. Upon use of all Heart Failure codes (ICD-9), sensitivity and specificity were 96.8 and 91.3%. CONCLUSIONS: Our results suggest that using computable phenotype to ascertain ADHF from the clinical notes contained within the electronic medical record are feasible and reliable. Our computable phenotype outperformed ICD-9 codes for the detection of ADHF.

Risk Factors for Persistent Cognitive Impairment After Critical Illness, Nested Case-Control Study.

OBJECTIVES: Persistent cognitive impairment after critical illness is an important healthcare problem forecasted to worsen in the near future. However, the epidemiology is insufficiently explored. We aimed to determine potentially modifiable risk factors during ICU hospitalization that play a significant role in developing persistent cognitive impairment. DESIGN: An observational case-control study. SETTINGS: Mayo Clinic ICUs between July 1, 2004, and November 20, 2015. PATIENTS: We conducted a study nested in a large cohort of 98,227 adult critically ill patients. Using previously validated computable phenotypes for dementia and cognitive impairment, we determined the onset of cognitive impairment relative to ICU hospitalization and associated risk factors. The primary endpoint of the study was new and persistent cognitive impairment documented between 3 and 24 months after ICU discharge. INTERVENTIONS: Unadjusted and adjusted analyses were performed to identify potentially modifiable risk factors during ICU hospitalization. MEASUREMENTS AND MAIN RESULTS: Among 21,923 unique patients identified as cognitively impaired (22% of the entire ICU cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction after the index ICU admission. Compared with age- and sex-matched ICU controls (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity Index, 6.2 vs 5.1; p < 0.01), and were more likely to have multiple ICU stays (22% vs 14%; p < 0.01). After adjustment for baseline differences, new and persistent cognitive dysfunction was associated with higher frequency of acute brain failure in the ICU, a higher exposure to severe hypotension, hypoxemia, hyperthermia, fluctuations in serum glucose, and treatment with quinolones or vancomycin. Association with sepsis observed in univariate analysis did not persist after adjustment. CONCLUSIONS: Cognitive dysfunction is highly prevalent in ICU patients. Incident new and persistent cognitive impairment is less common but important, potentially preventable problem after critical illness. Chronic comorbidities and number of ICU stays increase the risk of post-ICU cognitive dysfunction irrespective of age. Modifiable ICU exposures were identified as potential targets for future prevention trials.

Differentiating pulmonary transfusion reactions using recipient and transfusion factors.

BACKGROUND: It is increasingly recognized that recipient risk factors play a prominent role in possible transfusion-related acute lung injury (pTRALI) and transfusion-associated circulatory overload (TACO). We hypothesized that both transfusion and recipient factors including natriuretic peptides could be used to distinguish TRALI from TACO and pTRALI. STUDY DESIGN AND METHODS: We performed a post hoc analysis of a case-control study of pulmonary transfusion reactions conducted at the University of California at San Francisco and Mayo Clinic, Rochester. We evaluated clinical data and brain natriuretic peptides (BNP) levels drawn after transfusion in patients with TRALI (n = 21), pTRALI (n = 26), TACO (n = 22), and controls (n = 24). Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical and biomarker predictors in differentiating TRALI from TACO and pTRALI. RESULTS: We found that pTRALI and TACO were associated with older age, higher fluid balance, and elevated BNP levels relative to those of controls and TRALI. The following variables were useful in distinguishing cases of pTRALI and TACO from TRALI: age more than 70 years, BNP levels more than 1000 pg/mL, 24-hour fluid balance of more than 3 L, and a lower number of transfused blood components. Using the above variables, our logistic model had a 91% negative predictive value in the differential diagnosis of TRALI. CONCLUSIONS: Models incorporating readily available clinical and biomarker data can be used to differentiate transfusion-related respiratory complications. Additional studies examining recipient risk factors and the likelihood of TRALI may be useful in decision making regarding donor white blood cell antibody testing.

Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions.

BACKGROUND: Pulmonary transfusion reactions are important complications of blood transfusion, yet differentiating these clinical syndromes is diagnostically challenging. We hypothesized that biologic markers of inflammation could be used in conjunction with clinical predictors to distinguish transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and possible TRALI. STUDY DESIGN AND METHODS: In a nested case-control study performed at the University of California at San Francisco and Mayo Clinic, Rochester, we evaluated clinical data and blood samples drawn before and after transfusion in patients with TRALI (n = 70), possible TRALI (n = 48), TACO (n = 29), and controls (n = 147). Cytokines measured included granulocyte-macrophage-colony-stimulating factor, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-α. Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical predictors and laboratory markers in differentiating TACO, TRALI, and possible TRALI. RESULTS: Before and after transfusion, IL-6 and IL-8 were elevated in patients with TRALI and possible TRALI relative to controls, and IL-10 was elevated in patients with TACO and possible TRALI relative to that of TRALI and controls. For all pulmonary transfusion reactions, the combination of clinical variables and cytokine measurements displayed optimal diagnostic performance, and the model comparing TACO and TRALI correctly classified 92% of cases relative to expert panel diagnoses. CONCLUSIONS: Before transfusion, there is evidence of systemic inflammation in patients who develop TRALI and possible TRALI but not TACO. A predictive model incorporating readily available clinical and cytokine data effectively differentiated transfusion-related respiratory complications such as TRALI and TACO.

Characterizing the epidemiology of postoperative transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related death in the United States; however, it remains poorly characterized in surgical populations. To better inform perioperative transfusion practice, and to help mitigate perioperative TRALI, the authors aimed to better define its epidemiology before and after TRALI mitigation strategies were introduced. METHODS: This retrospective cohort study examined outcomes of adult patients undergoing noncardiac surgery with general anesthesia who received intraoperative transfusions during 2004 (n = 1,817) and 2011 (n = 1,562). The demographics and clinical characteristics of transfusion recipients, blood transfusion descriptors, and combined TRALI/possible TRALI incidence rates were evaluated. Univariate analyses were used to compare associations between patient characteristics, transfusion details, and TRALI mitigation strategies with TRALI/possible TRALI incidence rates in a before-and-after study design. RESULTS: The incidence of TRALI/possible TRALI was 1.3% (23 of 1,613) in 2004 versus 1.4% (22 of 1,562) in 2011 (P = 0.72), with comparable overall rates in males versus females (1.4% [23 of 1,613] vs. 1.2% [22 of 1,766]) (P = 0.65). Overall, thoracic (3.0% [4 of 133]), vascular (2.7% [10 of 375]), and transplant surgeries (2.2% [4 of 178]) carried the highest rates of TRALI/possible TRALI. Obstetric and gynecologic surgical patients had no TRALI episodes. TRALI/possible TRALI incidence increased with larger volumes of blood product transfused (P < 0.001). CONCLUSIONS: Perioperative TRALI/possible TRALI is more common than previously reported and its risk increases with greater volumes of blood component therapies. No significant reduction in the combined incidence of TRALI/possible TRALI occurred between 2004 and 2011, despite the introduction of TRALI mitigation strategies. Future efforts to identify specific risk factors for TRALI/possible TRALI in surgical populations may reduce the burden of this life-threatening complication.

Characterizing the epidemiology of perioperative transfusion-associated circulatory overload.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-related fatalities, but its incidence and associated patient and transfusion characteristics are poorly understood. To inform surgical transfusion practice and to begin mitigating perioperative TACO, the authors aimed to define its epidemiology. METHODS: In this retrospective cohort study, the medical records of adult patients undergoing noncardiac surgery with general anesthesia during 2004 or 2011 and receiving intraoperative transfusions were screened using an electronic algorithm for identification of TACO. Those patients who were screened as high probability for TACO underwent rigorous manual review. Univariate and multivariate analyses evaluated associations between patient and transfusion characteristics with TACO rates in a before-and-after study design. RESULTS: A total of 2,162 and 1,908 patients met study criteria for 2004 and 2011, respectively. The incidence of TACO was 5.5% (119 of 2,162) in 2004 versus 3.0% (57 of 1,908) in 2011 (P < 0.001), with comparable rates for men (4.8% [98 of 2,023]) and women (3.8% [78 of 2,047]) (P = 0.09). Overall, vascular (12.1% [60 of 497]), transplant (8.8% [17 of 193]), and thoracic surgeries (7.2% [10 of 138]) carried the highest TACO rates. Obstetric and gynecologic patients had the lowest rate (1.4% [4 of 295]). The incidence of TACO increased with volume transfused, advancing age, and total intraoperative fluid balance (all P < 0.001). CONCLUSIONS: The incidence of perioperative TACO is similar to previous estimates in nonsurgical populations. There was a reduction in TACO rate between 2004 and 2011, with incidence patterns remaining comparable in subgroup analyses. Future efforts exploring risk factors for TACO may guide preventive or therapeutic interventions, helping to further mitigate this transfusion complication.

Six-month quality-of-life and functional status of acute respiratory distress syndrome survivors compared to patients at risk: a population-based study.

INTRODUCTION: The long-term attributable burden related to acute respiratory distress syndrome (ARDS) is not fully investigated. The aim of this study is to evaluate the quality of life (QOL) and functional status at 6 months after hospitalization in patients at risk for ARDS who did and did not develop the syndrome. METHOD: This is a population-based prospective cohort study of adult patients from Olmsted County, Minnesota, with or at risk for ARDS hospitalized from October 2008 to July 2011. The primary outcomes were changes in QOL and functional status, measured through 12-Item Short Form Survey (SF-12) and Barthel Index (BI) respectively, from baseline to 6 months, compared between survivors who did and did not develop ARDS. RESULTS: Of 410 patients with or at risk for ARDS, 98 had baseline surveys collected and 67 responded to a 6-month survey (26 ARDS, 41 non-ARDS). Both ARDS and non-ARDS groups had lower physical component of SF-12 at baseline compared to general population (P < 0.001 for both). ARDS patients had poorer baseline functional status compared to non-ARDS (mean BI 80 ± 25 vs. 88 ± 22, P = 0.03). No significant differences were observed for the change between 6 months and baseline BI (delta 2.3 for ARDS vs. 2.0 for non-ARDS, P = 0.5), or mental (delta 2.7 vs. 2.4, P = 0.9) or physical (delta -3 vs. -3.3, P = 0.9) component of SF-12 between survivors with and without ARDS. CONCLUSION: In this population-based study, decreased QOL and functional status 6 months after hospitalization were largely explained by baseline condition, with similar recovery in survivors who did and did not develop ARDS.

Incidence of Adverse Events during Continuous Renal Replacement Therapy.

BACKGROUND/AIMS: The incidence of adverse events (AEs) in adults who receive continuous renal replacement therapy (CRRT) is unknown. We report the incidence of mechanical, metabolic, and hemodynamic CRRT AEs. METHODS: This is a retrospective study of all consecutive adult patients (≥18 years) who underwent CRRT from January 1, 2007 to December 31, 2009. RESULTS: Out of 595 patients who underwent CRRT, 366 (62%) were male and 500 (84%) were Caucasian. Regional citrate anticoagulation was used in 98.6% of all patients. The most common clinically significant electrolyte derangements were ionized hypocalcemia (22%), ionized hypercalcemia (23%), and hyperphosphatemia (44%). Almost all (97%) patients had at least one additional AE including new onset hypotension (within the first hour after CRRT initiation) (43%), hypothermia (44%), new onset arrhythmias (29%), new onset anemia (31%) and thrombocytopenia (40%). CONCLUSIONS: ICU patients who require CRRT have a high incidence of AEs. Although the extent to which these complications are attributable to CRRT is not known, clinicians need to be cautious and aware of their high prevalence in this patient population.

Intraoperative periprosthetic fractures associated with metacarpophalangeal joint arthroplasty.

PURPOSE: To assess the incidence of and identify risk factors for intraoperative periprosthetic fractures during primary and revision metacarpophalangeal (MCP) joint arthroplasty. METHODS: Through our institutional Joint Registry Database, we identified 818 MCP joint arthroplasties performed in 285 patients from 1998 to 2012, including 690 primary arthroplasties and 128 revision arthroplasties. Primary diagnoses included inflammatory arthritis (667), osteoarthritis (75), and posttraumatic arthritis (76). Periprosthetic fractures were identified through review of medical records. RESULTS: Intraoperative periprosthetic fractures occurred in 23 (3%) fingers (21 patients), including 19 primary and 4 revision arthroplasties. Twelve fractures required stabilization, 4 required only bone grafting, and 1 required both. The fractures occurred during broaching (12), implantation (10), or prior implant removal (1). Diabetes mellitus (DM), younger age, pyrocarbon implant insertion, and cementless fixation increased risk for intraoperative fracture. In particular, DM and the use of pyrocarbon implants significantly increased fracture risk. At 4 years (range, 1.3-10.2 y) average follow-up, no patient with intraoperative fracture had developed a subsequent fracture compared with 3 postoperative fractures in patients without intraoperative fractures. All fractures had healed by the time of the last follow-up. The 2- and 5-year implant survival rates were 96% and 80% in those with intraoperative fractures, respectively, which was not significantly different from those without an intraoperative fracture. When comparing patients with an intraoperative fracture with those without, there was an increased risk of postoperative MCP joint instability defined as implant dislocation. Patients with intraoperative fractures still had noteworthy improvements in their postoperative pain levels and pinch strengths. CONCLUSIONS: Intraoperative fractures occurred in 3% of MCP joint arthroplasties, including 3% of primary and 3% of revision arthroplasties. Increased risk for fracture was associated with the use of pyrocarbon implants, cementless fixation, and DM. Although these fractures did not appear to adversely affect implant survival, they were associated with increased risk of postoperative instability. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic III.

Brachial artery catheterization: an assessment of use patterns and associated complications.

BACKGROUND: Although studies have compared safety and outcomes of radial artery cannulation with other arterial catheterization locations, there is insufficient information describing brachial artery catheterization. In this study, we characterized the perioperative use patterns and the complication rates associated with brachial arterial catheterization and compared these outcomes with radial artery catheterization. METHODS: We performed a retrospective analysis of adult patients (age ≥18 years) undergoing surgical procedures at an academic medical center from January 1, 2008, to December 31, 2011. An institutional database containing information on anesthetic care was queried to identify all brachial artery catheterizations. Baseline characteristics, details relating to the surgical and catheterization procedures, and catheter-related complications were collected and compared with a random sample of patients receiving radial artery catheterization. RESULTS: We identified 858 patients receiving brachial catheterization perioperatively. An additional 3432 patients receiving radial catheterization were identified. Patients receiving brachial catheterization were more often women, had a lower body mass index, had more comorbidities, and had longer anesthetic and catheterization durations. Three vascular complications were identified in the cohort receiving brachial artery catheterization compared with 1 patient with a peripheral neuropathy in the radial artery catheterization cohort (unadjusted complication incidence [95% confidence intervals] brachial artery catheterization, 0.35% [0.12%-1.02%] vs radial artery catheterization, 0.03% [0.005%-0.16%], respectively; P = 0.030; relative risk [95% confidence interval] = 12.0 [1.7-83.4]). There were no catheter-related bloodstream infections. CONCLUSIONS: We found that brachial artery catheterization is used in more medically complex patients and for longer duration than radial artery catheterizations. Although the limited number of adverse outcomes precluded statistical adjustments in this investigation, the observed differences in complication rates between cannulation methods suggest that brachial artery catheterization may be a suitable alternative to radial artery catheterization in patients with complex medical comorbidities.

Electronic health record surveillance algorithms facilitate the detection of transfusion-related pulmonary complications.

BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are leading causes of transfusion-related mortality. Notably, poor syndrome recognition and underreporting likely result in an underestimate of their true attributable burden. We aimed to develop accurate electronic health record-based screening algorithms for improved detection of TRALI/transfused acute lung injury (ALI) and TACO. STUDY DESIGN AND METHODS: This was a retrospective observational study. The study cohort, identified from a previous National Institutes of Health-sponsored prospective investigation, included 223 transfused patients with TRALI, transfused ALI, TACO, or complication-free controls. Optimal case detection algorithms were identified using classification and regression tree (CART) analyses. Algorithm performance was evaluated with sensitivities, specificities, likelihood ratios, and overall misclassification rates. RESULTS: For TRALI/transfused ALI detection, CART analysis achieved a sensitivity and specificity of 83.9% (95% confidence interval [CI], 74.4%-90.4%) and 89.7% (95% CI, 80.3%-95.2%), respectively. For TACO, the sensitivity and specificity were 86.5% (95% CI, 73.6%-94.0%) and 92.3% (95% CI, 83.4%-96.8%), respectively. Reduced PaO2 /FiO2 ratios and the acquisition of posttransfusion chest radiographs were the primary determinants of case versus control status for both syndromes. Of true-positive cases identified using the screening algorithms (TRALI/transfused ALI, n = 78; TACO, n = 45), only 11 (14.1%) and five (11.1%) were reported to the blood bank by physicians, respectively. CONCLUSIONS: Electronic screening algorithms have shown good sensitivity and specificity for identifying patients with TRALI/transfused ALI and TACO at our institution. This supports the notion that active electronic surveillance may improve case identification, thereby providing a more accurate understanding of TRALI/transfused ALI and TACO epidemiology.

Lot-to-lot variability in HLA antibody screening using a multiplexed bead-based assay.

BACKGROUND: Identifying antibodies to HLA (anti-HLA) by solid-phase assays is used to screen blood donors to mitigate transfusion-related acute lung injury risk. Various cutoffs for detection assays have been proposed in the literature; however, these do not take into consideration lot-to-lot variability of commercially available assays. STUDY DESIGN AND METHODS: Samples from 93 nontransfused males were tested using five different lots of a multiplex bead-based anti-HLA detection kit. A subset of 17 samples was tested on 5 days using a single lot. An additional 96 samples from donations with varied anti-HLA levels were tested using kits from two different lots. Results were reported as a normalized background (NBG) ratio. RESULTS: For the 93 nontransfused donors, NBG values generated using the reference lot were significantly higher than those obtained with three of the four comparator lots. However, for the 96 samples with low-, moderate-, and higher-level anti-HLA, Class I (CL-I) values were 1.4 times lower and Class II (CL-II) values were 1.2 times lower using the reference versus comparator lot. For CL-I antibodies the between-lot standard deviation (SD) was 1.36 (95% confidence interval [CI], 1.19-1.60), while the between-day SD was 1.27 (95% CI, 1.08-1.52). Similarly, for CL-II antibodies the between-lot SD was 0.81 (95% CI, 0.70-0.95), while the between-day SD was 0.50 (95% CI, 0.43-0.60). CONCLUSIONS: There is interlot variability in the tested HLA detection assay as well as significant bias between lots. It may be reasonable to develop a new cutoff when a new lot is obtained.

Fresh red blood cell transfusion and short-term pulmonary, immunologic, and coagulation status: a randomized clinical trial.

RATIONALE: Transfusion-related pulmonary complications are leading causes of morbidity and mortality attributed to transfusion. Observational studies suggest an important role for red blood cell (RBC) storage duration in these adverse outcomes. OBJECTIVES: To evaluate the impact of RBC storage duration on short-term pulmonary function as well as immunologic and coagulation status in mechanically ventilated patients receiving RBC transfusion. METHODS: This is a double-blind, randomized, clinical trial comparing fresh (≤5 d of storage) versus standard issue single-unit RBC transfusion in adult intubated and mechanically ventilated patients. The primary outcome is the change in pulmonary gas exchange as assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio (ΔPa(O(2))/Fi(O(2))). Secondary outcomes include changes in immune and coagulation status. MEASUREMENTS AND MAIN RESULTS: Fifty patients were randomized to receive fresh RBCs and an additional 50 patients to standard issue RBCs. Median storage age was 4.0 days (interquartile range, 3.0-5.0) and 26.5 days (interquartile range, 21.0-36.0) in the fresh RBC group and standard issue RBC group, respectively. No differences were noted in the primary outcome of ΔPa(O(2))/Fi(O(2)) (difference between the mean ΔPa(O(2))/Fi(O(2)) in the standard issue RBC group vs. the fresh RBC group, -11.5; 95% confidence interval, -35.3 to 12.3; P = 0.22). Similarly, no significant differences were noted in markers of immunologic or coagulation status. CONCLUSIONS: In this randomized clinical trial, no differences were noted in early measures of pulmonary function or in immunologic or coagulation status when comparing fresh versus standard issue single-unit RBC transfusion. Clinical trial registered with ClinicalTrials.gov (NCT00751322).

Resolving the evolution of extant and extinct ruminants with high-throughput phylogenomics.

The Pecorans (higher ruminants) are believed to have rapidly speciated in the Mid-Eocene, resulting in five distinct extant families: Antilocapridae, Giraffidae, Moschidae, Cervidae, and Bovidae. Due to the rapid radiation, the Pecoran phylogeny has proven difficult to resolve, and 11 of the 15 possible rooted phylogenies describing ancestral relationships among the Antilocapridae, Giraffidae, Cervidae, and Bovidae have each been argued as representations of the true phylogeny. Here we demonstrate that a genome-wide single nucleotide polymorphism (SNP) genotyping platform designed for one species can be used to genotype ancient DNA from an extinct species and DNA from species diverged up to 29 million years ago and that the produced genotypes can be used to resolve the phylogeny for this rapidly radiated infraorder. We used a high-throughput assay with 54,693 SNP loci developed for Bos taurus taurus to rapidly genotype 678 individuals representing 61 Pecoran species. We produced a highly resolved phylogeny for this diverse group based upon 40,843 genome-wide SNP, which is five times as many informative characters as have previously been analyzed. We also establish a method to amplify and screen genomic information from extinct species, and place Bison priscus within the Bovidae. The quality of genotype calls and the placement of samples within a well-supported phylogeny may provide an important test for validating the fidelity and integrity of ancient samples. Finally, we constructed a phylogenomic network to accurately describe the relationships between 48 cattle breeds and facilitate inferences concerning the history of domestication and breed formation.

Polymorphisms at the PRNP gene influence susceptibility to chronic wasting disease in two species of deer (Odocoileus Spp.) in western Canada.

Chronic wasting disease (CWD) is increasingly prevalent in multiple wild mule (Odocoileus hemionus) and white-tailed deer (O. virginianus) herds in North America. CWD was first found in Canadian wild mule deer in Saskatchewan in 2000 and has since spread into the neighboring province of Alberta. The infectious agent for CWD is a misfolded prion protein encoded by the PRNP gene. Previous studies revealed association between PRNP genotype and susceptibility to CWD in both mule and white-tailed deer in other regions. To investigate this link in Canadian populations, PRNP gene sequence was examined in 166 CWD- and 83 CWD+ mule deer, and 197 CWD- and 30 CWD+ white-tailed deer from Saskatchewan and Alberta. Two variable sites were found in mule deer, and 15 in white-tailed deer. In both species PRNP genotype was associated with CWD status. Mule deer possessing at least one copy of the common allele at codon 20 were less likely to test positive for CWD than expected, given the frequency of this allele in the population. A variant at codon 96 in white-tailed deer was also linked with reduced incidence of CWD. A greater knowledge of the genetic sources of heterogeneity in CWD susceptibility may improve our understanding of the mechanisms underlying the CWD epidemic in western Canada.

Phylogeographic history and gene flow among giant Galápagos tortoises on southern Isabela Island.

Volcanic islands represent excellent models with which to study the effect of vicariance on colonization and dispersal, particularly when the evolution of genetic diversity mirrors the sequence of geological events that led to island formation. Phylogeographic inference, however, can be particularly challenging for recent dispersal events within islands, where the antagonistic effects of land bridge formation and vicariance can affect movements of organisms with limited dispersal ability. We investigated levels of genetic divergence and recovered signatures of dispersal events for 631 Galápagos giant tortoises across the volcanoes of Sierra Negra and Cerro Azul on the island of Isabela. These volcanoes are among the most recent formations in the Galápagos (<0.7 million years), and previous studies based on genetic and morphological data could not recover a consistent pattern of lineage sorting. We integrated nested clade analysis of mitochondrial DNA control region sequences, to infer historical patterns of colonization, and a novel Bayesian multilocus genotyping method for recovering evidence of recent migration across volcanoes using eleven microsatellite loci. These genetic studies illuminate taxonomic distinctions as well as provide guidance to possible repatriation programs aimed at countering the rapid population declines of these spectacular animals.

Derivation and validation of the automated search algorithms to identify cognitive impairment and dementia in electronic health records.

PURPOSE: Long-term cognitive impairment is a common and important problem in survivors of critical illness. We developed electronic search algorithms to identify cognitive impairment and dementia from the electronic medical records (EMRs) that provide opportunity for big data analysis. MATERIALS AND METHODS: Eligible patients met 2 criteria. First, they had a formal cognitive evaluation by The Mayo Clinic Study of Aging. Second, they were hospitalized in intensive care unit at our institution between 2006 and 2014. The "criterion standard" for diagnosis was formal cognitive evaluation supplemented by input from an expert neurologist. Using all available EMR data, we developed and improved our algorithms in the derivation cohort and validated them in the independent validation cohort. RESULTS: Of 993 participants who underwent formal cognitive testing and were hospitalized in intensive care unit, we selected 151 participants at random to form the derivation and validation cohorts. The automated electronic search algorithm for cognitive impairment was 94.3% sensitive and 93.0% specific. The search algorithms for dementia achieved respective sensitivity and specificity of 97% and 99%. EMR search algorithms significantly outperformed International Classification of Diseases codes. CONCLUSIONS: Automated EMR data extractions for cognitive impairment and dementia are reliable and accurate and can serve as acceptable and efficient alternatives to time-consuming manual data review.

Outcomes of cardiopulmonary resuscitation and predictors of survival in patients undergoing coronary angiography including percutaneous coronary interventions.

We studied the outcome of cardiopulmonary resuscitation (CPR) in patients undergoing coronary angiography (CA) and/or percutaneous coronary interventions (PCI). Of 51,985 CA and PCI patients treated between January 1, 1990, and December 31, 2000, 114 required CPR. Records were reviewed for relationships between patient characteristics and various procedures and short-term survival. Long-term survival was compared with that of a matched cohort of patients who did not have an arrest during catheterization and a matched cohort from the general Minnesota population. Over the 11-year period, the overall incidence of CPR was 21.9 per 10,000 procedures. This rate decreased from 33.9 per 10,000 before 1995 to 13.1 per 10,000 after 1995. Overall survival to hospital discharge after CPR was 56.1%. Survival to discharge was less frequent with a history of congestive heart failure, previous coronary artery bypass graft surgery, hemodynamic instability during the procedure, and with prolonged or emergent catheterizations. Pulseless electrical activity (versus asystole or ventricular fibrillation) indicated very poor short-term survival. Interestingly, short-term survival was not related to the extent of coronary artery disease. Long-term survival of patients who survived cardiac arrest was comparable to that of those who did not have arrest during catheterization. In conclusion, the incidence of periprocedural CPR during diagnostic or interventional coronary procedures decreased after 1995. Patients who received CPR in the cardiac catheterization lab have a remarkably frequent survival to hospital discharge rate. Long-term survival of these patients is only minimally reduced.

Prophylactic plasma transfusion for surgical patients with abnormal preoperative coagulation tests: a single-institution propensity-adjusted cohort study.

BACKGROUND: Perioperative haemorrhage negatively affects patient outcomes and results in substantial consumption of health-care resources. Plasma transfusions are often administered to address abnormal preoperative coagulation tests, with the hope to mitigate bleeding complications. We aimed to assess the associations between preoperative plasma transfusion and bleeding complications in patients with elevated international normalised ratio (INR) undergoing non-cardiac surgery. METHODS: We did an observational study in a consecutive sample of adult patients undergoing non-cardiac surgery with preoperative INR greater than or equal to 1·5. The exposure of interest was transfusion of preoperative plasma for elevated INR. The primary outcome was WHO grade 3 bleeding in the early perioperative period (from entry into the operating room until 24 h following exit from operating room). Hypotheses were tested with univariate and propensity-matched analyses. We did multiple sensitivity analyses to further evaluate the robustness of study findings. FINDINGS: Between Jan 1, 2008, and Dec 31, 2011, we identified 1234 (8·4%) of 14 743 patients who had an INR of 1·5 or above and were included in this investigation. Of 1234 study participants, 139 (11%) received a preoperative plasma transfusion. WHO grade 3 bleeding occurred in 73 (53%) of 139 patients who received preoperative plasma compared with 350 (32%) of 1095 patients who did not (odds ratio [OR] 2·35, 95% CI 1·65-3·36; p<0·0001). Among the propensity-matched cohort, 65 (52%) of 125 plasma recipients had WHO grade 3 bleeding compared with 97 (40%) of 242 of those who did not receive preoperative plasma (OR 1·75, 95% CI 1·09-2·81; p=0·021). Results from multiple sensitivity analyses were qualitatively similar. INTERPRETATION: Preoperative plasma transfusion for elevated international normalised ratios was associated with an increased frequency of perioperative bleeding complications. Findings were robust in the sensitivity analyses, suggestive that more conservative management of abnormal preoperative international normalised ratios is warranted. FUNDING: Mayo Clinic, National Institutes of Health.

Prophylactic Plasma Transfusion Before Interventional Radiology Procedures Is Not Associated With Reduced Bleeding Complications.

OBJECTIVE: To determine the association between prophylactic plasma transfusion and periprocedural red blood cell (RBC) transfusion rates in patients with elevated international normalized ratio (INR) values undergoing interventional radiology procedures. PATIENTS AND METHODS: In this retrospective cohort study, adult patients undergoing interventional radiology procedures with a preprocedural INR available within 30 days of the procedure during a study period of January 1, 2009, to December 31, 2013, were eligible for inclusion. Baseline characteristics, coagulation parameters, transfusion requirements, and procedural details were extracted. Univariate and multivariable propensity-matched analyses were used to assess the relationships between prophylactic plasma transfusion and the outcomes of interest, with a primary outcome assessed a priori of RBC transfusion occurring during the procedure or within the first 24 hours postprocedurally. RESULTS: A total of 18,204 study participants met inclusion criteria for this study, and 1803 (9.9%) had an INR of 1.5 or greater before their procedure. Of these 1803 patients, 196 patients (10.9%) received prophylactic plasma transfusion with a median time of 1.9 hours (interquartile range [IQR], 1.1-3.2 hours) between plasma transfusion initiation and procedure initiation. In multivariable propensity-matched analysis, plasma administration was associated with increased periprocedural RBC transfusions (odds ratio, 2.20; 95% CI, 1.38-3.50; P<.001) and postprocedural intensive care unit admission rates (odds ratio, 2.11; 95% CI, 1.41-3.14; P<.001) as compared with those who were not transfused preprocedurally. Similar relationships were seen at higher INR thresholds for plasma transfusion. CONCLUSION: In patients undergoing interventional radiology procedures, preprocedural plasma transfusions given in the setting of elevated INR values were associated with increased periprocedural RBC transfusions. Additional research is needed to clarify this potential association between preprocedural plasma transfusion and periprocedural RBC transfusion.