Increased Odds of Ventricular Arrhythmias Associated with Selective Serotonin Reuptake Inhibitor Use among the Pediatric and Young Adult Population: A Case-Control Study.

OBJECTIVE: To measure the association between selective serotonin reuptake inhibitor (SSRI) use and out-of-hospital ventricular arrhythmia among the pediatric and young adult population. STUDY DESIGN: Case-control study using US claims data from 2007 to 2018. Cases were subjects with at least 1 event between ages 2 and 24 years. Controls (matched 10:1 on index date, age, sex, and continuous enrollment) had no events during study period. Independent association between current SSRI use (prescription fill with continuous exposure ending on, or after, the index date) and incident out-of-hospital ventricular arrhythmia (hospitalization or emergency room encounter with primary diagnostic code for ventricular arrhythmia) was estimated using multivariable conditional logistic regression. Separate analyses were performed for pediatric (2-17 years of age) vs young adult (18-24 years of age) subjects and between citalopram/escitalopram vs other SSRIs. RESULTS: During the study period, 237 eligible cases were identified with 2370 matched controls. Cases were more likely to have government insurance and have a mental health, cardiac, or other complex chronic condition. Thirteen cases (5%) and 15 controls (<1%) had current SSRI exposure. After adjustment for mental health and chronic conditions, there was an increased odds of current SSRI use among cases compared with controls (OR 5.11, 95% CI 1.22-21.37). No difference was observed between pediatric and young adult ages, nor between citalopram/escitalopram and other SSRIs. CONCLUSIONS: These findings demonstrate increased odds of out-of-hospital ventricular arrhythmia associated with SSRI use in the pediatric and young adult population, suggesting a need for heightened awareness and ongoing monitoring of this potential adverse effect.

Opioid Prescribing After Discharge in a Previously Mechanically Ventilated, Opioid-Naïve Cohort.

BACKGROUND: Opioids are utilized for pain management during and after mechanical ventilation in the intensive care unit (ICU). OBJECTIVE: The purpose of this study was to determine the percentage of potentially unnecessary opioid prescriptions on discharge in previously opioid-naïve patients. METHODS: This retrospective cohort study included mechanically ventilated, opioid-naïve ICU patients who received opioids. The primary outcome of this study was the discrepancy between the amounts of opioids prescribed at discharge versus those likely required based on actual 24-hour prehospital discharge opioid requirements. RESULTS: A total of 71 patients were included. Of these, 63.3% (n = 45) of discharge prescriptions were in alignment with 24-hour predischarge requirements, and 36.7% (n = 26) of discharge prescriptions were in excess of calculated predischarge requirements. At discharge, 57.7% (n = 41) of patients received a nonopioid analgesic. Multivariable linear regression revealed that cardiothoracic ICU admission was associated with an increased risk of inappropriate discharge opioid prescribing, whereas a shorter duration of inpatient oral opioid therapy decreased risk of inappropriate discharge prescribing. CONCLUSION AND RELEVANCE: Opioid prescribing for previously mechanically ventilated patients warrants improvement as a part of the discharge planning process. Application of these data may aid in the reduction of opioid overprescribing at discharge after an ICU stay.

Validity of administrative claims-based algorithms for ventricular arrhythmia and cardiac arrest in the pediatric population.

PURPOSE: Identify administrative claims-based algorithms for capturing out-of-hospital ventricular arrhythmias (VA) and cardiac arrests (CA) due to cardiac causes in the pediatric population with high positive-predictive value (PPV). METHODS: Within a single pediatric center, a retrospective cohort of patients hospitalized or seen in the emergency room for VA or CA were identified from the electronic health records. Eligible encounters were blindly reviewed and linked to administrative data, including ICD-9/ICD-10 codes. Test characteristics, including PPV, for different diagnostic and procedure codes were generated using a 50% training sample. The gold standard was definite or suspected out-of-hospital VA or CA due to cardiac cause verified based on clinical criteria. Algorithms with the highest PPV were then applied to a 50% validation sample to validate performance. RESULTS: From 2004-2017, 598 encounters met eligibility criteria. 174 (29%) had an outcome of interest, with remainder being an inpatient event or CA due to other cause. Within the training sample (n = 263), VA codes in primary position had a PPV 94% (95%CI 81%-99%) with low sensitivity (44%, 95%CI 33%-56%). CA codes in any position or VA codes in nonprimary positions had low PPV (18%-19%, 31% respectively). Applying the top three performing algorithms to the validation sample (n = 252) yielded similar PPV values. CONCLUSIONS: Contrary to adults, algorithms including a CA code do not perform well for identifying out-of-hospital VA and CA due to cardiac cause in the pediatric populations. Researchers should be aware of the potential implications for future pediatric drug safety studies for these outcomes.

Are Evidence-based Practices Associated With Effective Prevention of Hospital-acquired Pressure Ulcers in US Academic Medical Centers?

BACKGROUND: In 2008, the Centers for Medicare and Medicaid Services (CMS) established nonpayment policies resulting from costliness of hospital-acquired pressure ulcers (HAPUs) to hospitals. This prompted hospitals to adopt quality improvement (QI) interventions that increase use of evidence-based practices (EBPs) for HAPU prevention. OBJECTIVE: To evaluate the longitudinal impact of CMS policy and QI adoption on HAPU rates. MATERIALS AND METHODS: We characterized longitudinal adoption of 25 QI interventions that support EBPs through hospital leadership, staff, information technology, and performance and improvement. Quarterly counts of HAPU incidence and inpatient characteristics were collected from 55 University HealthSystem Consortium hospitals between 2007 and 2012. Mixed-effects regression models tested the longitudinal association of CMS policy, HAPU coding, and QI on HAPU rates. The models assumed level-2 random intercepts and random effects for CMS policy and EBP implementation to account for between-hospital variability in HAPU incidence. RESULTS: Controlling for all 25 QI interventions, specific updates to EBPs for HAPU prevention had a significant, though modest reduction on HAPU rates (-1.86 cases/quarter; P=0.002) and the effect of CMS nonpayment policy on HAPU prevention was much greater (-11.32 cases/quarter; P<0.001). CONCLUSIONS: HAPU rates were significantly lower after changes in CMS reimbursement. Reductions are associated with hospital-wide implementation of EBPs for HAPU prevention. Given that administrative data were used, it remains unknown whether these improvements were due to changes in coding or improved quality of care.

Comparison of antidepressant classes and the risk and time course of suicide attempts in adults: propensity matched, retrospective cohort study.

BACKGROUND: Placebo-controlled clinical trials have led to concern over possible increased risk of suicide-related events in some populations exposed to antidepressants. AIMS: To evaluate the risk of suicide attempts by antidepressant drug class and the presence or absence of depression. METHOD: A retrospective propensity-matched new-user cohort study was used to compare participants with incident depression classified by antidepressant treatment with each other and with the general population. RESULTS: Among the treated group, the suicide attempt rate peaked in the month prior to diagnosis then decreased steadily over the next 6 months. Among the pharmacologically untreated group, the highest rate was seen in the second month after diagnosis. Cohorts with depression had significantly higher suicide attempt risk than the general population, but the treated group did not differ significantly from the untreated group. CONCLUSIONS: Patients on antidepressants did not have significantly higher risk compared with untreated patients. No significant differences were observed for patients treated with individual serotonin-noradrenaline reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) or by class (SSRI v. SNRI cohorts).

The depth, duration, and degree of outpatient pediatric polypharmacy in Colorado fee-for-service Medicaid patients.

BACKGROUND AND OBJECTIVES: Outpatient pediatric polypharmacy is poorly characterized. Identification of at-risk populations has clinical implications for pharmacy case management programs. We described the degree of exposure to polypharmacy using parameters of depth (concurrent medication count) and duration, reported commonly dispensed medications and exposure to three example potential drug-drug interactions by different depths of polypharmacy, and determined patient characteristics associated with exposure to increased degrees (a function of depth and duration) of polypharmacy. METHODS: Retrospective cohort study of Colorado fee-for-service Medicaid patients aged <18 years with 12 months of continuous enrollment. We calculated depth of polypharmacy using daily concurrent medication counts and duration of polypharmacy using days exposed to a certain depth. Multinomial logistic regression was used to assess patient characteristics associated with different degrees of polypharmacy. RESULTS: Of 242 230 patients, 35% percent were exposed to any depth of polypharmacy, most commonly to anti-infective medications. Patients with higher depth polypharmacy were exposed to less common medications (psychotropic drugs, anticonvulsants, cardiovascular agents, and opioids) and to higher rates of exposure to potential drug-drug interactions. Of 47 972 patients exposed to ≥3 concurrent medications, 50% were exposed for <15 days, 25% for 15-38 days, 15% for 39-111 days, and 10% for 112-327 days. High-degree polypharmacy was associated with increasing age, male gender, and presence of a complex chronic condition. CONCLUSIONS: Outpatient pediatric polypharmacy occurs to a substantial degree for a small but vulnerable population of children, who may be candidates for pharmacy case management. We must determine whether increased exposure to high-degree polypharmacy causes harm.

Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents.

PURPOSE: In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding. METHODS: We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding. RESULTS: For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone. CONCLUSIONS: Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth.

Outcomes associated with corticosteroid dosage in critically ill patients with acute exacerbations of chronic obstructive pulmonary disease.

RATIONALE: Studies evaluating corticosteroid (CS) dosing for patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have largely excluded patients admitted directly to the intensive care unit (ICU), and none have evaluated the effect of CS dosing regimens on mortality. OBJECTIVES: To examine the effectiveness and safety of lower- versus high-dose CS in patients admitted to the ICU with an AECOPD. METHODS: This pharmacoepidemiologic cohort study evaluated ICU patients with AECOPD admitted to one of 473 hospitals and treated with CS within the first 2 days between January 1, 2003 and December 31, 2008. Patients were grouped into lower-dose (methylprednisolone, ≤240 mg/d) or high-dose (methylprednisolone, >240 mg/d) groups based on CS dosage on hospital Day 1 or 2. The primary outcome was hospital mortality. MEASUREMENTS AND MAIN RESULTS: A total of 17,239 patients were included; 6,156 (36%) were in the lower-dose and 11,083 (64%) in the high-dose CS group. After propensity score matching and adjustment for unbalanced covariates, lower-dose CS was not associated with a significant reduction in mortality (odds ratio, 0.85; 95% confidence interval [CI], 0.71-1.01; P = 0.06), but it was associated with reduced hospital (-0.44 d; 95% CI, -0.67 to -0.21; P < 0.01) and ICU (-0.31 d; 95% CI, -0.46 to -0.16; P < 0.01) length-of-stay, hospital costs (-$2,559; 95% CI, -$4,508 to -$609; P = 0.01), length of invasive ventilation (-0.29 d; 95% CI, -0.52 to -0.06; P = 0.01), need for insulin therapy (22.7% vs. 25.1%; P < 0.01), and fungal infections (3.3% vs. 4.4%; P < 0.01). CONCLUSIONS: Two-thirds of patients admitted to the ICU with an AECOPD are treated with high doses of CS that are associated with worse outcomes and more frequent adverse effects. Lower dosage strategies should be encouraged for patients admitted to the ICU and the optimum dose should be determined through clinical trials.

Comparative effectiveness of quality improvement interventions for pressure ulcer prevention in academic medical centers in the United States.

BACKGROUND: Prevention of pressure ulcers, one of the hospital-acquired conditions (HACs) targeted by the 2008 nonpayment policy of the Centers for Medicare & Medicaid Services (CMS), is a critical issue. This study was conducted to determine the comparative effectiveness of quality improvement (QI) interventions associated with reduced hospital-acquired pressure ulcer (HAPU) rates. METHODS: In an quasi-experimental design, interrupted time series analyses were conducted to determine the correlation between HAPU incidence rates and adoption of QI interventions. Among University HealthSystem Consortium hospitals, 55 academic medical centers were surveyed from September 2007 through February 2012 for adoption patterns of QI interventions for pressure ulcer prevention, and hospital-level data for 5,208 pressure ulcer cases were analyzed. Between- and within-hospital reduction significance was tested with t-tests post-CMS policy intervention. RESULTS: Fifty-three (96%) of the 55 hospitals used QI interventions for pressure ulcer prevention. The effect size analysis identified five effective interventions that each reduced pressure ulcer rates by greater than 1 case per 1,000 patient discharges per quarter: leadership initiatives, visual tools, pressure ulcer staging, skin care, and patient nutrition. The greatest reductions in rates occurred earlier in the adoption process (p<.05). CONCLUSIONS: Five QI interventions had clinically meaningful associations with reduced stage III and IV HAPU incidence rates in 55 academic medical centers. These QI interventions can be used in support of an evidence-based prevention protocol for pressure ulcers. Hospitals can not only use these findings from this study as part of a QI bundle for preventing HAPUs.

Hospital-Acquired Pressure Ulcers at Academic Medical Centers in the United States, 2008-2012: Tracking Changes Since the CMS Nonpayment Policy.

BACKGROUND: In 2007, the Centers for Medicare & Medicaid Services (CMS) announced its intention to no longer reimburse hospitals for costs associated with hospital-acquired pressure ulcers (HAPUs) and a list of other hospital-acquired conditions (HACs), which was followed by enactment of the nonpayment policy in October 2008. This study was conducted to define changes in HAPU incidence and variance since 2008. METHODS: In a retrospective observational study, HAPU cases were identified at 210 University HealthSystem Consortium (UHC) academic medical centers in the United States. HAPU incidence rates were calculated as a ratio of HAPU cases to the total number of UHC inpatients between the first quarter of 2008 and the second quarter of 2012. HAPU cases were defined by multiple criteria: not present on admission (POA); coded for stage III or IV pressure ulcers; and a length of stay greater than four days. RESULTS: Among the UHC hospitals between 2008 and June 2012, 10,386 HAPU cases were identified among 4.08 million inpatients. The HAPU incidence rate decreased significantly from 11.8 cases per 1,000 inpatients in 2008 to 0.8 cases per 1,000 in 2012 (p < .001; 95% confidence interval: 8.39-8.56). Among HAPU cases were trends of more elderly patients, greater case-mix index, and more surgical cases. The analysis of covariance model identified CMS non-payment policy as a significant covariate of changing trends in HAPU incidence rates. CONCLUSIONS: HAPU incidence rates decreased significantly among 210 UHC AMCs after the enactment of the CMS nonpayment policy. The hospitals appeared to be reacting efficiently to economic policy incentives by improving prevention efforts.

Factors Influencing Adoption of Hospital-Acquired Pressure Ulcer Prevention Programs in US Academic Medical Centers.

PURPOSE: Recent data show a decrease in hospital-acquired pressure ulcers (PUs) throughout US hospitals; these changes may be associated with increased success in implementing evidence-based practices for PU prevention. The purpose of this study was to identify wound care nurse perceptions of the primary factors that influenced the overall reduction of PUs. DESIGN: Cross-sectional descriptive survey. SUBJECTS AND SETTING: Surveys were sent to wound care nurses at 98 University HealthSystem Consortium (UHC) hospitals. The UHC consists of more than 120 academic medical centers and affiliated facilities across the United States. Responses solicited from this survey represented a geographically diverse set of hospitals from less than 200 beds to more than 1000 beds. INSTRUMENT: The survey questionnaire used a framework of 7 internal and 5 external influential factors for implementing evidence-based practices for PU prevention. Internal influential factors queried included availability of nurse specialists, high nursing job turnover, high PU rates, and prevention campaigns. External influential factors included data sharing, Medicare nonpayment policy, and applications for Magnet recognition. METHODS: Hospital-acquired PU prevention experts at UHC hospitals were contacted through the Wound, Ostomy and Continence Nurses Society membership directory to complete the questionnaire. Consenting participants were e-mailed a disclosure and online questionnaire; they were also sent monthly reminders until they either responded to the survey or declined participation. RESULTS: Fifty-five respondents (59% response rate) indicated several internal factors that influenced evidence-based practice: hospital prevention campaigns; the availability of nursing specialists; and the level of preventive knowledge among hospital staff. External influential factors included financial concerns; application for Magnet recognition; data sharing among peer institutions; and regulatory issues. CONCLUSIONS: These findings suggest that the Centers for Medicare & Medicaid Services nonpayment policy influenced a large majority of hospital's changes in practice. The availability of nursing specialists for wound consult influenced hospitals internally. These factors are informative of the impact policy has on changes in hospital prioritization of adopting evidence-based practices for PU prevention.

Increased Adoption of Quality Improvement Interventions to Implement Evidence-Based Practices for Pressure Ulcer Prevention in U.S. Academic Medical Centers.

OBJECTIVE: In 2008, the U.S. Centers for Medicare and Medicaid Services enacted a nonpayment policy for stage III and IV hospital-acquired pressure ulcers (HAPUs), which incentivized hospitals to improve prevention efforts. In response, hospitals looked for ways to support implementation of evidence-based practices for HAPU prevention, such as adoption of quality improvement (QI) interventions. The objective of this study was to quantify adoption patterns of QI interventions for supporting evidence-based practices for HAPU prevention. METHODS: This study surveyed wound care specialists working at hospitals within the University HealthSystem Consortium. A questionnaire was used to retrospectively describe QI adoption patterns according to 25 HAPU-specific QI interventions into four domains: leadership, staff, information technology (IT), and performance and improvement. Respondents indicated QI interventions implemented between 2007 and 2012 to the nearest quarter and year. Descriptive statistics defined patterns of QI adoption. A t-test and statistical process control chart established statistically significant increase in adoption following nonpayment policy enactment in October 2008. Increase are described in terms of scope (number of QI domains employed) and scale (number of QI interventions within domains). RESULTS: Fifty-three of the 55 hospitals surveyed reported implementing QI interventions for HAPU prevention. Leadership interventions were most frequent, increasing in scope from 40% to 63% between 2008 and 2012; "annual programs to promote pressure ulcer prevention" showed the greatest increase in scale. Staff interventions increased in scope from 32% to 53%; "frequent consult driven huddles" showed the greatest increase in scale. IT interventions increased in scope from 31% to 55%. Performance and improvement interventions increased in scope from 18% to 40%, with "new skin care products . . ." increasing the most. LINKING EVIDENCE TO ACTION: Academic medical centers increased adoption of QI interventions following changes in nonpayment policy. These QI interventions supported adherence to implementation of pressure ulcer prevention protocols. Changes in payment policies for prevention are effective in QI efforts.

A framework of quality improvement interventions to implement evidence-based practices for pressure ulcer prevention.

PURPOSE: To enhance the learner's competence with knowledge about a framework of quality improvement (QI) interventions to implement evidence-based practices for pressure ulcer (PrU) prevention. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Summarize the process of creating and initiating the best-practice framework of QI for PrU prevention.2. Identify the domains and QI interventions for the best-practice framework of QI for PrU prevention. Pressure ulcer (PrU) prevention is a priority issue in US hospitals. The National Pressure Ulcer Advisory Panel endorses an evidence-based practice (EBP) protocol to help prevent PrUs. Effective implementation of EBPs requires systematic change of existing care units. Quality improvement interventions offer a mechanism of change to existing structures in order to effectively implement EBPs for PrU prevention. The best-practice framework developed by Nelson et al is a useful model of quality improvement interventions that targets process improvement in 4 domains: leadership, staff, information and information technology, and performance and improvement. At 2 academic medical centers, the best-practice framework was shown to physicians, nurses, and health services researchers. Their insight was used to modify the best-practice framework as a reference tool for quality improvement interventions in PrU prevention. The revised framework includes 25 elements across 4 domains. Many of these elements support EBPs for PrU prevention, such as updates in PrU staging and risk assessment. The best-practice framework offers a reference point to initiating a bundle of quality improvement interventions in support of EBPs. Hospitals and clinicians tasked with quality improvement efforts can use this framework to problem-solve PrU prevention and other critical issues.

Comparative safety of selective serotonin reuptake inhibitors among pediatric users with respect to adverse cardiac events.

PURPOSE: This study aims to perform a comparative safety study assessing the risk of ventricular arrhythmia, cardiac arrest, or sudden death among pediatric selective serotonin reuptake inhibitor (SSRI) users. METHODS: Using US claims data from 1997 to 2009, new pediatric (age < 18 years) users of SSRI monotherapy were identified. Adverse cardiac outcomes occurring within 12 months of SSRI initiation were identified using a previously validated International Classification of Disease, ninth edition algorithm. Cox proportional hazard analysis was used to estimate the risk for each SSRI, using fluoxetine as the referent group, adjusting for the propensity to receive an individual SSRI, demographics, and exposure covariates. RESULTS: Over the study period, 113,714 subjects met the inclusion criteria and contributed 40,639 person-years of SSRI exposure time. Sertraline (33%) and fluoxetine (29%) were the most commonly prescribed SSRIs. Forty events occurred within 12 months of SSRI initiation. The crude incidence rate was highest for escitalopram (19.5/10,000 person-years) and lowest for fluoxetine (4.2/10,000 person-years). The median time to event ranged from 45 to 86 days. The adjusted risk of adverse event, relative to fluoxetine, was highest for citalopram Hazard Ratio (HR) = 3.53, 95% confidence interval [CI] = 1.09­11.46) and escitalopram (HR = 3.30, 95%CI = 1.08­10.14) and lowest for paroxetine (HR = 1.34, 95%CI = 0.30­5.99) and sertraline (HR = 2.14, 95%CI = 0.75­6.16). CONCLUSIONS: The incidence of adverse cardiac events among pediatric SSRI users was low. However, the risk of an adverse outcome was higher for citalopram and escitalopram users as compared with fluoxetine users. Future studies should focus on confirming these findings and identifying modifying risk factors to optimize medication selection for this population.

Risk of suicide attempt in asthmatic children and young adults prescribed leukotriene-modifying agents: a nested case-control study.

BACKGROUND: The US Food and Drug Administration has issued safety alerts about leukotriene receptor-modifying agents and suicidality/suicide, but because these were based on case reports, there is controversy about the association. OBJECTIVE: We conducted a nested case-control study to determine the association between leukotriene-modifying agents (LTMAs) and attempted suicide among asthmatic children and young adults. METHODS: Cases and control subjects were from a cohort of asthmatic patients aged 5 to 24 years who were new users of LTMAs or other asthma medications. Data were from an insurance claims database. Cases were defined as those with a suicide attempt (SA) occurring after exposure to asthma medication. Control subjects were persons at risk and were selected by using incidence density sampling in a 10:1 match. Conditional logistic regression was used to determine the association between LTMA exposure and the risk of attempted suicide adjusted for important covariates. RESULTS: We identified 344 cases and 3438 matched control subjects. Cases were more likely than control subjects to have risk factors for suicide. We found that current use of any LTMA was not associated with increased risk of an SA; in fact, the direction of effect was the opposite (adjusted odd ratio, 0.70; 95% CI, 0.36-1.39). CONCLUSION: In this analysis we found that use of LTMAs was not associated with an increased risk of SAs in children, adolescents, and young adults with asthma. Further research needs to be conducted to more fully understand the association between LTMAs and suicide, particularly in subpopulations.

Thrombosis risk factor assessment and implications for prevention in critically ill children.

OBJECTIVES: To describe nursing compliance with a computer-based pediatric thrombosis risk assessment tool; to generate an estimate of risk factors present in our population; and to explore relationships between risk factors and confirmed thrombotic events. DESIGN: Institutional review board-approved prospective, observational cohort study. SETTING: Pediatric intensive care unit within a tertiary care children's hospital. PATIENTS: All infants and children admitted to the pediatric intensive care unit during a 6-month study period (January 1, 2010-June 30, 2010). MEASUREMENTS AND MAIN RESULTS: Eight hundred admissions were enrolled, representing 742 patients. Thrombosis risk assessment scores were recorded for 707 admissions (88% of total). Mean age = 6.95 ± 6 yrs, mean weight = 28 ± 23 kg, 45% female. A total of 32 thrombi (14 prehospital and 18 in-hospital) were present in the study group. This translated to an overall occurrence rate of 4.3% (1.9% for prehospital and 2.4% for in-hospital). Logistic regression identified that for every 1-point increase in total thrombosis score, the risk of developing a symptomatic thrombus increased by 1.57-fold (95% confidence interval 0.192-5.5) to 2.12-fold (95% confidence interval 0.175-18.34), for prehospital and in-hospital thrombi, respectively (p < .05). The most important risk factors identified for development of any thrombus were thrombophilia (acquired or inherited) (p < .001), presence of a central catheter (p = .01), and age <1 or >14 yrs (p = .052). CONCLUSIONS: Incorporation of a scoring system into the bedside nursing assessment flow sheet was successful and identified children at risk for in-hospital thrombosis. The overall score appears to be most indicative of thrombus risk. These data may serve as a platform for future development of routine screening and possible interventional trials in critically ill children.

Small area variation and geographic and patient-specific determinants of metabolic testing in antipsychotic users.

PURPOSE: The American Diabetes Association and American Psychiatric Association recommend metabolic monitoring for all patients using second-generation antipsychotic (SGA) drugs. We estimated glucose and lipid testing rates among SGA-users from three state Medicaid programs and investigated small area variation and patient and geographic determinants of testing. METHODS: A retrospective new-user cohort study using Medicaid claims data from California, Missouri, and Oregon was conducted among 30,563 patients in 207 counties starting SGA medication September 2004-December 2005. Adjusted odds ratios for state, county, and patient factors associated with testing were calculated from multivariable hierarchical logistic regression models. RESULTS: Mean 6-month testing rates were 51.6% (glucose) and 26.2% (lipids). Screening rates were positively associated with the number of Type 2 diabetes risk factors (RF) present: glucose -39% (0 RF) to 82% (5 RF); lipids -13% (0 RF) to 66% (5 RF). A four-fold difference in glucose testing rates (21-85%) and a greater than six-fold difference in lipid testing rates (0-62%) were observed between counties. In the adjusted regression models, age, cardiometabolic co-morbidity (diabetes, dyslipidemia), serious mental illness, persistent use of SGAs, and frequency of non-psychiatric medical office visits were significant determinants of glucose and lipid testing. Lipid testing was more likely for children and adults in California, as was glucose testing for children. CONCLUSIONS: Glucose and lipid testing among SGA-users varied significantly between states, counties, and by patient characteristics. More effort is needed to understand provider and system reasons for testing disparities in order to inform risk management quality improvement interventions.

Comparative effectiveness research in DARTNet primary care practices: point of care data collection on hypoglycemia and over-the-counter and herbal use among patients diagnosed with diabetes.

BACKGROUND: The Distributed Ambulatory Research in Therapeutics Network (DARTNet) is a federated network of electronic health record (EHR) data, designed as a platform for next-generation comparative effectiveness research in real-world settings. DARTNet links information from nonintegrated primary care clinics that use EHRs to deliver ambulatory care to overcome limitations with traditional observational research. OBJECTIVE: Test the ability to conduct a remote, electronic point of care study in DARTNet practices by prompting clinic staff to obtain specific information during a patient encounter. RESEARCH DESIGN: Prospective survey of patients identified through queries of clinical data repositories in federated network organizations. On patient visit, survey is triggered and data are relinked to the EHR, de-identified, and copied for evaluation. SUBJECTS: Adult patients diagnosed with diabetes mellitus that scheduled a clinic visit for any reason in a 2-week period in DARTNet primary care practices. MEASURES: Survey on hypoglycemic events (past month) and over-the-counter and herbal supplement use. RESULTS: DARTNet facilitated point of care data collection triggered by an electronic prompt for additional information at a patient visit. More than one-third of respondents (33% response rate) reported either mild (45%) or severe hypoglycemic events (5%) in the month before the survey; only 3 of those were also coded using the ICD-9 (a significant difference in detection rates 37% vs. 1%). Nearly one-quarter of patients reported taking an OTC/herbal, 4% specifically for the treatment of symptoms of diabetes. CONCLUSIONS: Prospective data collection is feasible in DARTNet and can enable comparative effectiveness and safety research.

An electronic practice-based network for observational comparative effectiveness research.

The Distributed Ambulatory Research in Therapeutics Network (DARTNet) is a federated network of electronic health data from 8 organizations representing more than 500 clinicians and more than 400 000 patients. DARTNet was designed to increase knowledge of the comparative effectiveness of prescription medications and medical devices. Traditional observational comparative effectiveness research is conducted using large data sets, such as claims databases. Such databases do not provide important clinical information that is critical to understanding comparative effectiveness. By linking electronic health records, laboratory and imaging data, and administrative data from diverse and geographically disparate patients, DARTNet provides important new insight into the comparative effectiveness of oral diabetes medications, and it is ready for expansion to further enable effectiveness research.

Effects of a 3-Tier Pharmacy Benefit Design on the Prescription Purchasing Behavior of Individuals With Chronic Disease.

OBJECTIVE: To evaluate the impact of 3-tier (copayment) pharmacy benefit structures on medication utilization behavior. METHODS: A pretest-posttest quasi-experimental design was employed. Chronic disease sufferers (N=8,132) from a health plan were classified into the following groups: (a) 2-tier copayment moving to a 3-tier structure, ("converting" group), (b) 2-tier staying in a 2-tier structure and, (c) 3-tier staying in a 3-tier structure. The latter 2 were "comparison" groups. Two 7-month time periods were determined: the "preperiod" (June through December 2000) and the "postperiod" (January through July 2001) for a change in pharmacy benefit structure. Pharmacy claims data were used for data collection. Statistical analyses included bivariate tests to evaluate predifferences and postdifferences across study groups. Maximum likelihood estimates from a repeated measures model were used to examine changes in formulary compliance and generic use rates. Discontinuation of nonformulary medications was evaluated using logistic regression. RESULTS: Controlling for demographics, number of comorbidities, disease state, and pharmacy benefit structure, the formulary compliance rate increased by 5.6% for the converting group. No significant increases were seen for the comparison groups. Generic use rates increased by 6 to 8 absolute percentage points for all groups (3.3% to 4.9 % adjusted rates). Converting group members were 1.76 times more likely to discontinue their nonformulary medication than those in the 2-tier comparison group and 1.49 times more likely than those in the 3-tier comparison group. CONCLUSIONS: These findings suggest that shifting individuals from a 2-tier to a 3-tier drug benefit copayment structure resulted in changes in medication utilization. Decision makers need to balance these changes with the potential dissatisfaction that members may express in paying higher copayments. DISCLOSURES: Funding for this research was provided by Merck and Company through the Academic Medicine and Managed Care Forum and was obtained by authors Kavita V. Nair, Robert J. Valuck, Pamela Wolfe, Julie M. Ganther, and Marianne M. McCollum. Nair served as principal author of the study. Study concept and design was contributed by Nair, Valuck, Wolfe, Ganther, McCollum, and author Sonya J. Lewis. Analysis and interpretation of data and drafting of the manuscript were primarily the work of Nair and Wolfe, and all authors contributed to the critical revision of the manuscript. Statistical expertise was contributed by Wolfe. Administrative, technical, and/or material support was provided by Mark Enders.