Fang Ju Lin

Effects of clinical decision support on venous thromboembolism risk assessment, prophylaxis, and prevention at a university teaching hospital

PURPOSE The implementation of a mandatory assessment of risk for venous thromboembolism (VTE) in a health systems electronic medical record (EMR) and clinical decision-support (CDS) system was evaluated to measure its effect on the use of pharmacologic prophylaxis and the occurrence of VTE and bleeding events. METHODS A commercially available CDS system was used in designing the automated CDS intervention. During computerized order entry, the system delivered alerts prompting clinician risk assessment and also delivered alerts under circumstances suggesting less-than-optimal prophylaxis. Rates of pharmacologic prophylaxis, clinically diagnosed hospital-acquired VTE, and hospital-acquired bleeding events were measured during one year before and one year after implementation. RESULTS After adjustment for patient age, sex, and high-risk comorbidities, the data showed a postimplementation increase in the percentage of patients who received pharmacologic prophylaxis at some time during their admission from 25.9% to 36.8% (p < 0.001). The rate of VTE for the entire hospital did not change significantly, but a significant reduction among patients on medical units was observed, from 0.55% to 0.33% (p = 0.02). There was no increase in either major or minor bleeding events. CONCLUSION Without increasing the risk of bleeding, a CDS system requiring clinicians to document VTE risk assessment in the EMR promoted improved rates of pharmacologic prophylaxis at any time during an admission and a decreased risk of VTE in general medical patients but not all adult patients.

Evaluation of content on EQ-5D as compared to disease-specific utility measures

PurposeThe goal of this study was to appraise the extent of unique content on disease-specific preference-based measures (DSPMs) when contrasted with the EQ-5D using published studies and to inform whether EQ-5D could be inadequate as a utility measure in its content coverage for a given disease-specific application.MethodsA structured search of published literature was performed using PubMed and EMBASE/Medline database from Jan 1, 1990 to Mar 31, 2011. Articles were eligible for inclusion if algorithms were developed to convert components from disease-specific measures into utility scores.ResultsOf 1,029 articles identified, 50 studies satisfied the inclusion criteria. The most frequent conditions where DSPMs were developed included cancer (12 studies), coronary artery disease (4 studies), osteoarthritis, rheumatoid arthritis (3 studies of each), obesity, and stroke (2 studies of each). Most studies involved mapping items or scores from disease-specific non-preference-based measures onto a preference-based measure of health such as the EQ-5D. A substantial number of DSPMs appeared to include unique content not covered by EQ-5D dimensions.ConclusionsSeveral conditions were identified as potential areas where the richness of the EQ-5D descriptive system could be enhanced. It is yet unclear whether added dimension(s) would contribute unique explained variance to a utility score. Given the resources required to rigorously develop a utility measure, the need for such measures should be carefully vetted.

Chest computed tomography for penetrating thoracic trauma after normal screening chest roentgenogram.

BACKGROUND Chest computed tomography (CCT) is a method of screening for intrathoracic injuries in hemodynamically stable patients with penetrating thoracic trauma. The objective of this study was to examine the changes in utilization of CCT over time and evaluate its contribution to guiding therapeutic intervention. METHODS A level 1 trauma center registry was queried between 2006 and 2011. Patients undergoing CCT in the emergency department after penetrating thoracic trauma as well as patients undergoing thoracic operations for penetrating thoracic trauma were identified. Patient demographics, operative indications, use of CCT, injuries, and hospital admissions were analyzed. RESULTS In all, 617 patients had CCTs performed, of whom 61.1% (371 of 617) had a normal screening plain chest radiograph (CXR). In 14.0% (51 of 371) of these cases, the CCT revealed findings not detected on screening CXR. The majority of these injuries were occult pneumothoraces or hemothoraces (84.3%; 43 of 51), of which 27 (62.8%) underwent tube thoracostomy. In only 0.5% (2 of 371), did the results of CCT alone lead to an operative indication: exploration for hemopericardium. The use of CCT in our patients significantly increased overall (28.8% to 71.4%) as well as after a normal screening CXR (23.3% to 74.6%) over the study period. CONCLUSIONS The use of CCT for penetrating thoracic trauma increased 3.5-fold during the study period with a concurrent increase in findings of uncertain clinical significance. Patients with a normal screening CXR should be triaged with 3-hour delayed CXR, serial physical examinations, and focused assessment with sonography for trauma; and CCT should only be used selectively as a diagnostic modality.

Overexpression of RalBP1 in colorectal cancer is an independent predictor of poor survival and early tumor relapse

The non-ABC transport protein RalBP1 has been shown to be overexpressed in various cancer cell lines and implicated in the process of metastasis formation, but its expression in tissue samples and prognostic significance has not been shown. In this study matched tumor-mucosa tissue samples from 78 CRC patients were investigated. The RalBP1 mRNA and protein levels were quantified by real-time quantitative PCR (qPCR) and ELISA. RalBP1 was found to be overexpressed in tumor at the mRNA level both overall (p = 0.027), and for stages I (p = 0.024), II (p = 0.038) and IV (p = 0.004). At the protein level, RalBP1 was only significantly overexpressed in stage IV patients (p = 0.018). Expression of RalBP1 mRNA and protein were inversely correlated (r = 0.4173; p = 0.0004). Multivariate Cox regression analysis including sex, age, stage, grade, and nodal status as covariates showed that overexpression of RalBP1 protein, but not mRNA, was an independent predictor of both decreased disease free survival (p = 0.016, RR = 6.892) and overall survival (p = 0.039, RR = 5.986). These results suggest that RalBP1 protein is an independent predictor of poor survival and early relapse for CRC patients. Owing to its multifunctional intermediary role in cell survival, chemotherapeutic resistance, and metastasis formation, RalBP1 represents a promising novel therapeutic target.

Cost-utility analysis of genotype-guided antiplatelet therapy in patients with moderate-to-high risk acute coronary syndrome and planned percutaneous coronary intervention

Background Prasugrel is recommended over clopidogrel in poor/intermediate CYP2C19 metabolizers with acute coronary syndrome (ACS) and planned percutaneous coronary intervention (PCI), reducing the risk of ischemic events. CYP2C19 genetic testing can guide antiplatelet therapy in ACS patients. Objective The purpose of this study was to evaluate the cost-utility of genotype-guided treatment, compared with prasugrel or generic clopidogrel treatment without genotyping, from the US healthcare provider’s perspective. Methods A decision model was developed to project lifetime economic and humanistic burden associated with clinical outcomes (myocardial infarction [MI], stroke and major bleeding) for the three strategies in patients with ACS. Probabilities, costs and age-adjusted quality of life were identified through systematic literature review. Incremental cost-utility ratios (ICURs) were calculated for the treatment strategies, with quality-adjusted life years (QALYs) as the primary effectiveness outcome. Relative risk of developing myocardial infarction and stroke between patients with and without variant CYP2C19 when receiving clopidogrel were estimated to be 1.34 and 3.66, respectively. One-way and probabilistic sensitivity analyses were performed. Results Clopidogrel cost USD19,147 and provided 10.03 QALYs versus prasugrel (USD21,425, 10.04 QALYs) and genotype-guided therapy (USD19,231, 10.05 QALYs). The ICUR of genotype-guided therapy compared with clopidogrel was USD4,200. Genotype-guided therapy provided more QALYs at lower costs compared with prasugrel. Results were sensitive to the cost of clopidogrel and relative risk of myocardial infarction and stroke between CYP2C19 variant vs. non-variant. Net monetary benefit curves showed that genotype-guided therapy had at least 70% likelihood of being the most cost-effective alternative at a willingness-to-pay of USD100,000/QALY. In comparison with clopidogrel, prasugrel therapy was more cost-effective with <21% certainty at willingness-to-pay of >USD170,000/QALY. Conclusions Our modeling analyses suggest that genotype-guided therapy is a cost-effective strategy in patients with acute coronary syndrome undergoing planned percutaneous coronary intervention.

Utilization of Cardiothoracic Surgeons for Operative Penetrating Thoracic Trauma and Its Impact on Clinical Outcomes

BACKGROUND Large series reporting outcomes for penetrating thoracic trauma have identified injury pattern and injury severity scoring as predictors of poor outcome. However, the impact of surgical expertise on patient outcomes has not been previously investigated. We sought to determine how often board-certified cardiothoracic surgeons are utilized for operative thoracic trauma and whether this has an effect on patient outcomes. METHODS A level I trauma center registry was queried between 2003 and 2011. Records of patients undergoing surgery as a result of penetrating thoracic trauma were retrospectively reviewed. Patient demographics, injuries, injury severity, utilization of a cardiothoracic surgical operative consult and outcomes were recorded. Patients operated on by cardiothoracic surgeons were compared with patients operated on by trauma surgeons using stepwise multivariate analyses to determine the factors associated with utilization of cardiothoracic surgeons for operative thoracic trauma and survival. RESULTS Cardiothoracic surgeons were used in 73.0% of cases (162 of 222) over the study period. The use of cardiothoracic surgeons increased incrementally both overall (38.5% to 73.9%), and for emergent/urgent cases (31.8% to 73.3%). When comparing patients undergoing operation on an emergent/urgent basis by cardiothoracic versus trauma surgeons, there was no significant difference with regard to demographics, mechanism of injury, injury severity scoring, or surgical morbidity. Stepwise logistic regression showed the presence of a cardiothoracic surgeon to be independently associated with survival (odds ratio 4.70; p = 0.019). CONCLUSIONS Use of cardiothoracic surgeons for operative thoracic trauma increased over the study period. Outcomes for severely injured patients with elevated chest injury scores or decreased revised trauma scores may be improved with appropriate operative consultation with a board-certified cardiothoracic surgeon.

Residual Risk Factors to Predict Major Adverse Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with and without Diabetes Mellitus

A prospective observational study was conducted to investigate the residual risk factors to predict recurrence of major adverse cardiovascular events (MACE) in atherosclerotic cardiovascular disease (ASCVD) patients with a high prevalence under lipid-lowering therapy, particularly in the subpopulations of diabetic and nondiabetic individuals. A total of 5,483 adults (with a mean age of 66.4 and 73.3% male) with established coronary heart disease, cerebrovascular disease, or peripheral artery disease were identified from the T-SPARCLE multi-center registry. Of them, 38.6% had diabetes. The residual risk factors for MACE are divergent in these atherosclerotic patients with and without diabetes. In diabetic subpopulation, the risk of MACE was significantly increased with heart failure (HF), chronic kidney disease (CKD) stage 4–5 (vs. stage 1–2), without beta blocker use, and higher non-HDL-C, after controlling for covariates including statin use and the intensity of therapy. Increased LDL-C and TG levels were also associated with increased risk, but to a much less extent. Among nondiabetic individuals, HF, CKD stage 4–5, and history of myocardial infarction were the significant independent predictors of MACE. It is suggested that ASCVD patients with concomitant diabetes need stricter control of lipid, particularly non-HDL-C levels, to reduce cardiovascular risk when on statin therapy.

Dosing patterns and medication adherence in bipolar disorder patients treated with lurasidone: a US retrospective claims database analysis

Background: The aim of this study was to describe dosing patterns and medication adherence among bipolar patients who initiated lurasidone in a real-world setting. Methods: Adult bipolar patients who initiated lurasidone between 1 November 2010 and 31 December 2012 (index period) with 6-month pre- and post-index continuous enrollment were identified from the IMS RWD Adjudicated Claims US database. Patients were grouped by starting lurasidone daily dose: 20 mg (7.1%), 40 mg (62.2%), 60–80 mg (28.7%), and 120–160 mg (2.1%). Patient characteristics were compared across doses using Cochran–Armitage trend tests. Multivariable ordinal logistic regression assessed the association between initial lurasidone dose and patient characteristics. Medication adherence was measured using medication possession ratio (MPR). Results: Of 1114 adult bipolar patients (mean age 40.6 years, 70.6% female), 90% initiated lurasidone at 40 mg or 80 mg/day (mean 51.9 mg/day). Of these, 16.2% initiated lurasidone as monotherapy. Mean lurasidone maintenance dose was 55.2 mg/day and mean MPR was 0.53 [standard deviation (SD) = 0.34] over the 6-month follow up. Substance use, hyperglycemia, obesity, and prior antipsychotic use were associated with higher initial lurasidone doses (p < 0.05). Odds of a 20 mg/day increase in initial lurasidone dose was 1.6-times higher for patients with substance use [95% confidence interval (CI): 1.16−2.24], 2.6-times higher with hyperglycemia problems (95% CI: 1.15−5.83), 1.7-times higher with obesity (95% CI: 1.05−2.60), and 1.3 (95% CI: 1.01−1.78) and 1.8-times higher (95% CI: 1.17−2.86) with prior use of second- and first-generation antipsychotics, respectively. Conclusions: This real-world analysis of bipolar patients indicated that 40 mg or 80 mg/day were the most common starting doses of lurasidone. A majority of patients used concomitant psychiatric medications (polypharmacy). Higher doses of lurasidone were prescribed to patients with comorbidities or prior antipsychotic use. Adherence to lurasidone was comparable to or better than antipsychotic adherence reported in bipolar disorder literature.

Age-associated impact on presentation and outcome for penetrating thoracic trauma in the adult and pediatric patient populations

BACKGROUND Studies reporting on penetrating thoracic trauma in the pediatric population have been limited by small numbers and implied differences with the adult population. Our objectives were to report on a large cohort of pediatric patients presenting with penetrating thoracic trauma and to determine age-related impacts on management and outcome through comparison with an adult cohort. METHODS A Level I trauma center registry was queried between 2006 and 2012. All patients presenting with penetrating thoracic trauma were identified. Patient demographics, injury mechanism, injury severity, admission physiology, and outcome were recorded. Patients were compared, and outcomes were analyzed based on age at presentation, with patients 17 years or younger defining our pediatric cohort. RESULTS A total of 1,423 patients with penetrating thoracic trauma were admitted during the study period. Two hundred twenty patients (15.5%) were pediatric, with 205 being adolescents (13–17 years) and 15 being children (⩽12 years). In terms of management for the pediatric population, tube thoracostomy alone was needed in 32.7% (72 of 220), whereas operative thoracic exploration was performed in 20.0% (44 of 220). Overall mortality was 13.6% (30 of 220). There was no significant difference between the pediatric and adult population with regard to injury mechanism or severity, need for therapeutic intervention, operative approach, use of emergency department thoracotomy, or outcome. Stepwise logistic regression failed to identify age as a predictor for the need for either therapeutic intervention or mortality between the two age groups as a whole. However, subgroup analysis revealed that being 12 years or younger (odds ratio, 3.84; 95% confidence interval, 1.29–11.4) was an independent predictor of mortality. CONCLUSION Management of traumatic penetrating thoracic injuries in terms of the need for therapeutic intervention and operative approach was similar between the adult and pediatric populations. Mortality from penetrating thoracic trauma can be predicted based on injury severity, the use of emergency department thoracotomy, and admission physiology for adolescents and adults. Children may be at increased risk for poor outcome independent of injury severity. LEVEL OF EVIDENCE Epidemiologic study, level III.

Evaluation of changes in guidelines for medication management of stable chronic obstructive pulmonary disease.

RATIONALE, AIMS AND OBJECTIVES The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines are well-known international clinical practice guidelines for chronic obstructive pulmonary disease (COPD). The objective of this study was to examine how treatment recommendations and the quality of supporting evidence for pharmacologic management of stable COPD have evolved since the initial guidance issued in 2001. METHODS Recommendations in the 2001 and 2011 GOLD guidelines, along with the evidence grades (i.e. A, B, C, D), were identified and abstracted. We determined the distribution and evolution of recommendations across levels of evidence and treatment categories over time. RESULTS There were 35 and 54 recommendations identified in the 2001 and 2011 guidelines, respectively. Twenty-six recommendations were common to the 2001 and 2011 guidelines, with eight having the same evidence grade in both versions and three having a grade change (one upgraded and two downgraded). Twenty-eight new recommendations were added in 2011. Bronchodilators, glucocorticosteroids, and phosphodiesterase-4 inhibitors are the classes of pharmacologic treatment with the most prominent changes regarding emerging evidence and the number of recommendations. Approximately 45% of the graded recommendations were supported by well-designed randomized controlled trials, i.e. grade A. CONCLUSIONS The GOLD guideline recommendations have changed considerably over the past 11 years, which reflects a dynamic evidence base and perhaps a change in the way guideline developers view the evidence to inform recommendations. Given the large number of recommendations with lower grade levels, there continues to be substantial opportunity to inform gaps in the evidence base with high-quality studies.