Santiago Romero-Brufau

Widely used track and trigger scores: Are they ready for automation in practice?

INTRODUCTIONnEarly Warning Scores (EWS) are widely used for early recognition of patient deterioration. Automated alarm/alerts have been recommended as a desirable characteristic for detection systems of patient deterioration. We undertook a comparative analysis of performance characteristics of common EWS methods to assess how they would function if automated.nnnMETHODSnWe evaluated the most widely used EWS systems (MEWS, SEWS, GMEWS, Worthing, ViEWS and NEWS) and the Rapid Response Team (RRT) activation criteria in use in our institution. We compared their ability to predict the composite outcome of Resuscitation call, RRS activation or unplanned transfer to the ICU, in a time-dependent manner (3, 8, 12, 24 and 36 h after the observation) by determining the sensitivity, specificity and positive predictive values (PPV). We used a large vital signs database (6,948,689 unique time points) from 34,898 unique consecutive hospitalized patients.nnnRESULTSnPPVs ranged from less than 0.01 (Worthing, 3 h) to 0.21 (GMEWS, 36 h). Sensitivity ranged from 0.07 (GMEWS, 3 h) to 0.75 (ViEWS, 36 h). Used in an automated fashion, these would correspond to 1040-215,020 false positive alerts per year.nnnCONCLUSIONSnWhen the evaluation is performed in a time-sensitive manner, the most widely used weighted track-and-trigger scores do not offer good predictive capabilities for use as criteria for an automated alarm system. For the implementation of an automated alarm system, better criteria need to be developed and validated before implementation.

Why the C-statistic is not informative to evaluate early warning scores and what metrics to use

Metrics typically used to report the performance of an early warning score (EWS), such as the area under the receiver operator characteristic curve or C-statistic, are not useful for pre-implementation analyses. Because physiological deterioration has an extremely low prevalence of 0.02 per patient-day, these metrics can be misleading. We discuss the statistical reasoning behind this statement and present a novel alternative metric more adequate to operationalize an EWS. We suggest that pre-implementation evaluation of EWSs should include at least two metrics: sensitivity; and either the positive predictive value, number needed to evaluate, or estimated rate of alerts. We also argue the importance of reporting each individual cutoff value.

Outcomes After Coronary Stent Implantation in Patients With Metal Allergy

Background— Clinical outcomes after stent placement in patients with a history of metal allergy remain incompletely understood. We performed a single-center retrospective study to evaluate such outcomes. Methods and Results— Twenty-nine allergic patients who underwent coronary stent implantation were compared with a nonallergic group (n=250) matched for demographics and a propensity score for allergy to metal. Hypersensitivity to nickel was reported in 26 of 29 and chromium in 9 of 29. Patch testing performed in 11 of 29 patients was positive in all. Comparing allergy versus control subjects, there were no differences in number of segments treated (1.4±0.7 versus 1.5±0.7), stents placed (1.7±1.1 versus 1.6±0.9), and frequency of drug-eluting stent usage (52% versus 60%). In-hospital death (0% versus 0%), myocardial infarction (MI, 4% versus 3%, P=0.27), and 30-day death (3% versus 0%, P=0.53) and MI (3% versus 4%, P=0.71) were statistically similar. There were no differences in 4-year death (12% versus 13%), target lesion revascularization (TLR, 13 versus 17%, P=0.54), or death/MI/TLR (24% versus 34%, P=0.20). Clinically driven repeat angiography in 12 of 29 allergy patients revealed binary restenosis rates of 27% in bare metal stents and 0% in drug-eluting stents, with mean diameter in-stent restenosis of 36% and 8%, respectively. There was no change in circulating eosinophil and lymphocyte counts after stenting in the allergy group (0.19–0.20, P=0.67, and 1.90–1.79, P=0.59, respectively). Conclusions— A history of metal allergy was not associated with adverse early or late outcomes in this single-center study.

Development and validation of an electronic medical record-based alert score for detection of inpatient deterioration outside the ICU

BACKGROUNDnPatients in general medical-surgical wards who experience unplanned transfer to the intensive care unit (ICU) show evidence of physiologic derangement 6-24h prior to their deterioration. With increasing availability of electronic medical records (EMRs), automated early warning scores (EWSs) are becoming feasible.nnnOBJECTIVEnTo describe the development and performance of an automated EWS based on EMR data.nnnMATERIALS AND METHODSnWe used a discrete-time logistic regression model to obtain an hourly risk score to predict unplanned transfer to the ICU within the next 12h. The model was based on hospitalization episodes from all adult patients (18years) admitted to 21 Kaiser Permanente Northern California (KPNC) hospitals from 1/1/2010 to 12/31/2013. Eligible patients met these entry criteria: initial hospitalization occurred at a KPNC hospital; the hospitalization was not for childbirth; and the EMR had been operational at the hospital for at least 3months. We evaluated the performance of this risk score, called Advanced Alert Monitor (AAM) and compared it against two other EWSs (eCART and NEWS) in terms of their sensitivity, specificity, negative predictive value, positive predictive value, and area under the receiver operator characteristic curve (c statistic).nnnRESULTSnA total of 649,418 hospitalization episodes involving 374,838 patients met inclusion criteria, with 19,153 of the episodes experiencing at least one outcome. The analysis data set had 48,723,248 hourly observations. Predictors included physiologic data (laboratory tests and vital signs); neurological status; severity of illness and longitudinal comorbidity indices; care directives; and health services indicators (e.g. elapsed length of stay). AAM showed better performance compared to NEWS and eCART in all the metrics and prediction intervals. The AAM AUC was 0.82 compared to 0.79 and 0.76 for eCART and NEWS, respectively. Using a threshold that generated 1 alert per day in a unit with a patient census of 35, the sensitivity of AAM was 49% (95% CI: 47.6-50.3%) compared to the sensitivities of eCART and NEWS scores of 44% (42.3-45.1) and 40% (38.2-40.9), respectively. For all three scores, about half of alerts occurred within 12h of the event, and almost two thirds within 24h of the event.nnnCONCLUSIONnThe AAM score is an example of a score that takes advantage of multiple data streams now available in modern EMRs. It highlights the ability to harness complex algorithms to maximize signal extraction. The main challenge in the future is to develop detection approaches for patients in whom data are sparser because their baseline risk is lower.

Psoriasis lesions are associated with specific types of emotions. Emotional profile in psoriasis

BackgroundAt present there is still controversy about the relationship between emotional stress and psoriasis lesions. Most of the published literature does not include the broad spectrum of emotional response.ObjectiveThe aim of this study was to evaluate the association between skin lesions and emotional state in a large sample of patients with psoriasis.Methods823 psoriasis patients were recruited (mean age 45.9 years, 55.7% female) and answered two online questionnaires: lesion severity and current extension were evaluated using a self-administered psoriasis severity index (SAPASI); emotional state was assessed using the positive and negative affect schedule (PANAS). Second order factors were calculated and correlated with the SAPASI.ResultsWe found positive associations between the extent and severity of skin lesions and the negative and submissive emotions, a negative correlation with dominance emotions and no association with positive emotions.ConclusionsOur data supports the relationship between emotions and skin lesions. It also allows for discrimination of the associations between psoriasis lesions and the specific type of emotions.

Free Functioning Gracilis Muscle Transfer for Elbow Flexion Reconstruction after Traumatic Adult Brachial Pan-Plexus Injury: Where Is the Optimal Distal Tendon Attachment for Elbow Flexion?

Background: Reconstruction after pan-plexus root avulsions often includes gracilis free functioning muscle transfer. For elbow flexion reconstruction, the free functioning muscle transfer distal tendon is inserted into the biceps tendon or more distally (i.e., flexor digitorum profundus/flexor pollicis longus tendons) for combined elbow and finger flexion; the theoretical drawback of the latter approach is weaker elbow flexion. The authors compared elbow flexion strength with a biceps tendon versus a flexor digitorum profundus/flexor pollicis longus tendon attachment to determine which insertion point resulted in better elbow flexion. Methods: Thirty-nine patients underwent free functioning muscle transfer with either a biceps tendon or a distal attachment. Groups were compared on postoperative elbow flexion strength, preoperative and postoperative Disabilities of the Arm, Shoulder, and Hand questionnaire scores, range of motion, and other surgical and demographic characteristics. A biomechanical analysis simulating different tendon attachments determined which reconstruction resulted in optimal elbow flexion mechanics. Results: Distal tendon attachment was associated with M3 or M4 elbow flexion and greater range of motion compared with the biceps tendon attachment (p < 0.05). There were no statistically significant improvements in Disabilities of the Arm, Shoulder, and Hand questionnaire scores. Biomechanical analysis demonstrated that all distal tendon attachments studied generated a 15 to 30 percent greater torque compared with the biceps tendon attachment; this was true for attachments either at the flexor digitorum profundus/flexor pollicis longus tendon, or directly at the radius at 10 cm or 15 cm from the elbow axis of rotation. Conclusions: The flexor digitorum profundus/flexor pollicis longus tendon attachment of the gracilis free functioning muscle transfer distal tendon was superior in achieving elbow flexion strength. Patients with only elbow flexion reconstruction may also benefit from a flexor digitorum profundus/flexor pollicis longus tendon attachment or from a more distal attachment to the radius. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Antitumoral gene-based strategy involving nitric oxide synthase type III overexpression in hepatocellular carcinoma.

Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or green fluorescent protein, and luciferase complementary DNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenovirus and Hepa 1–6 cells were used for in vitro and in vivo experiments. Adenoviruses were administered through the tail vein 2 weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8, -9 and -3 activities in cultured Hepa 1–6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by Nω-nitro-l-arginine methyl ester hydrochloride, p53 and CD95 small interfering RNA. AFP-NOS-3/RSV-luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

Evaluating automated rules for rapid response system alarm triggers in medical and surgical patients

BACKGROUND: The use of rapid response systems (RRS), which were designed to bring clinicians with critical care expertise to the bedside to prevent unnecessary deaths, has increased. RRS rely on accurate detection of acute deterioration events. Early warning scores (EWS) have been used for this purpose but were developed using heterogeneous populations. Predictive performance may differ in medical vs surgical patients. OBJECTIVE: To evaluate the performance of published EWS in medical vs surgical patient populations. DESIGN: Retrospective cohort study. SETTING: Two tertiary care academic medical center hospitals in the Midwest totaling more than 1500 beds. PATIENTS: All patients discharged from January to December 2011. INTERVENTION: None. MEASUREMENTS: Time‐stamped longitudinal database of patient variables and outcomes, categorized as surgical or medical. Outcomes included unscheduled transfers to the intensive care unit, activation of the RRS, and calls for cardiorespiratory resuscitation (“resuscitation call”). The EWS were calculated and updated with every new patient variable entry over time. Scores were considered accurate if they predicted an outcome in the following 24 hours. RESULTS: All EWS demonstrated higher performance within the medical population as compared to surgical: higher positive predictive value (P < .0001 for all scores) and sensitivity (P < .0001 for all scores). All EWS had positive predictive values below 25%. CONCLUSIONS: The overall poor performance of the evaluated EWS was marginally better in medical patients when compared to surgical patients.

Nitric Oxide Synthase Type III Overexpression By Gene Therapy Exerts Antitumoral Activity In Mouse Hepatocellular Carcinoma

Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. Hepa 1-6 cells were used for in vitro and in vivo experiments. The first generation adenovirus was designed to overexpress NOS-3 (or GFP) and luciferase cDNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenoviruses were administered through the tail vein two weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-Luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8 activity in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by l-NAME or p53 siRNA. The tail vein infusion of AFP-NOS- 3/RSV-Luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

Clinical Decision Making: A Framework for Predicting Rx Response

Over seventy percent of Americans take at least one form of prescription medication, with twenty percent taking more than five. The numbers emphasize how important it is for clinicians to understand the effects of the medication and whether these medications are effective. In this paper we propose a data driven framework to predict the effectiveness of medication on a patient, specifically in the case of diabetes. Our dataset contains claims data from 1.5 million patients. A heuristic was established to evaluate the effectiveness of Metformin using a set of three criteria. Decision trees and random forests were used to create prediction models on the training data and select features. The model was able to correctly predict whether a patient responded well to the medication with approximately 80% accuracy and an F1-measure of approximately 90%.