Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy.

OBJECTIVE: Rhythm- and rate-control therapies are an essential part of atrial fibrillation (AF) management; however, the use of existing agents is often limited by the occurrence of adverse events. The aim of this study was to evaluate suspected adverse events and adverse event monitoring, and associated medical costs, in patients receiving AF rhythm-control and/or rate-control therapy. RESEARCH DESIGN AND METHODS: This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from 2002-2006. Patients hospitalized for AF (primary diagnosis), and who had at least 365 days' enrollment before and after the initial (index) AF hospitalization, were included in the analysis. Suspected AF therapy-related adverse events and function tests for adverse event monitoring were identified according to pre-specified diagnosis codes/procedures, and examined over the 12 months following discharge from the index hospitalization. Events/function tests had to have occurred within 90 days of a claim for AF therapy to be considered a suspected adverse event/adverse event monitoring. RESULTS: Of 4174 AF patients meeting the study criteria, 3323 received AF drugs; 428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765 combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients had a suspected adverse event and/or function test for adverse event monitoring (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined rhythm/rate-control). Suspected cardiovascular adverse events were the most common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and endocrine events (5.9%). Overall, suspected adverse events/function tests were associated with mean annual per-patient costs of $3089 ($1750 with rhythm-control, $2041 with rate control, and $6755 with combined rhythm/rate-control). LIMITATIONS: As a retrospective analysis, the study is subject to potential selection bias, while its reliance on diagnostic codes for identification of AF and suspected adverse events is a source of potential investigator error. A direct cause-effect relationship between suspected adverse events/function tests and AF therapy cannot be confirmed based on the claims data available. CONCLUSIONS: The incidence of suspected adverse events and adverse event monitoring during AF rhythm-control and/or rate-control therapy is high. Costs associated with adverse events and adverse event monitoring are likely to add considerably to the overall burden of AF management.

Incidence and temporal pattern of hospital readmissions for patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is prevalent and has a high cost burden. Among the main drivers of cost is inpatient care; however, little is known about patterns of hospital readmissions for AF. OBJECTIVE: To evaluate the incidence and temporal pattern of readmission in AF patients. METHODS: This retrospective, cohort analysis used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database for 2002-2006. Patients hospitalized for AF (primary discharge diagnosis) were identified. Data on the first readmission for AF over 1 year following an index hospitalization were analyzed for chronic AF (any AF-related claims in 1 year before index hospitalization) and newly-diagnosed AF patients (no prior AF-related claims). RESULTS: Overall, 4174 patients hospitalized with primary AF were identified; 1637 had chronic AF and 2537 newly-diagnosed AF. Mean age of chronic AF patients was 62.4 years and 61.2% were male; for newly-diagnosed AF, mean age was 61.4 years and 57.8% were male. In the year following index hospitalization, 12.5% of chronic AF patients were readmitted for AF, with a mean time to readmission of 142.5 days (median 108 days). Among newly-diagnosed AF patients, 10.1% were readmitted for AF, with a mean time to readmission of 133.8 days (median 112 days). For chronic AF, 17.6%, 43.4%, and 65.8% of readmissions occurred within 1, 3, and 6 months, respectively, versus 22.7%, 44.5%, and 67.2%, respectively, for newly-diagnosed AF. LIMITATIONS: Limited data were available on patients' clinical profile, treatment patterns, or the reasons for hospitalization/readmission. The term chronic AF only captured patients with a history of AF and data were not available to classify patients according to the presence of paroxysmal, permanent, or persistent AF. CONCLUSIONS: Patients with newly-diagnosed or chronic AF are often readmitted in the year following hospitalization with most readmissions occurring within 6 months of the index hospitalization.

Hospital-based costs associated with venous thromboembolism treatment regimens.

INTRODUCTION: Venous thromboembolism (VTE) poses a significant health and economic burden in US hospitals. Clinical guidelines for acute VTE treatment recommend antithrombotic therapy (at least 5 days) with low molecular weight heparin (LMWH) or unfractionated heparin (UFH). With upcoming US national performance measures requiring successful implementation of evidence-based therapy, cost considerations for anticoagulant choice are of increasing importance to hospitals. METHODS: This retrospective cohort analysis utilizes discharge records from a large real-world US population (January 2002 to December 2006) to provide total, direct, inpatient medical costs associated with LMWH and UFH for acute VTE treatment. Furthermore, for both LMWH and UFH discharges, we compare VTE-related readmission rates at 30 and 90 days after discharge. RESULTS: In total, 57 131 discharges were identified (57.7% LMWH; 42.3% UFH). After adjustment for covariates, including age, severity of illness, and length of stay, total direct medical costs per hospital discharge for UFH were $3476.22 vs. $3056.42 for LMWH (P < 0.0001; difference $420). Costs were significantly higher in the UFH group for most cost categories. Notably, drug acquisition cost was higher for LMWH. LMWH treatment was 12% [odds ratio (OR) 0.876; P < 0.001] and 10% (OR 0.895; P = 0.0006) less likely to result in VTE readmission within 30 and 90 days, respectively. CONCLUSIONS: This study provides the first large, real-world analysis of the total direct medical costs of treating VTE in-hospital. It confirms that, despite higher drug acquisition costs, LMWH is cost-saving compared with UFH in the inpatient setting, and is associated with a lower VTE readmission rate at 30 and 90 days than is UFH.

Evidence-based interventions to improve patient compliance with antihypertensive and lipid-lowering medications.

The MEDLINE database was searched from 1972 to June 2002 to identify studies of interventions designed to improve compliance with antihypertensive or lipid-lowering medications. Studies were required to employ a controlled design, follow patients for >or=6 months and measure compliance by a method other than patient self-report. The literature review yielded 62 studies describing 79 interventions. Overall, 56% of interventions were reported to improve patient compliance. When only those studies meeting minimum criteria for methodological quality were considered, 22 interventions remained and 12 were recommended, because they demonstrated a significant improvement in compliance. Recommended interventions included fixed-dose combination drugs, once-daily or once-weekly dosing schedules, unit-dose packaging, educational counselling by telephone, case management by pharmacists, treatment in pharmacist- or nurse-operated disease management clinics, mailed refill reminders, self-monitoring, dose-tailoring, rewards and various combination strategies. Personalised, patient-focused programs that involved frequent contact with health professionals or a combination of interventions were the most effective at improving compliance. Less-intensive strategies, such as prescribing products that simplify the medication regimen or sending refill reminders, achieved smaller improvements in compliance but may be cost-effective due to their low cost.

Dedicated asthma center improves the quality of care and resource utilization for pediatric asthma: a multicenter study.

OBJECTIVES: To determine the relative effectiveness of pediatric asthma care among patients treated by a dedicated asthma center (AC) vs children who use the emergency department (ED) as a site of primary asthma care. METHODS: A retrospective case-control design was used. A random sample of AC cases was selected from a designated comprehensive AC over a 12-month period. Concurrent ED control patients were identified from all cases of pediatric asthma from five urban hospitals based on two or more ED visits. Cases and controls were matched (1:2) based on age and National Heart, Lung, and Blood Institute (NHLBI) asthma severity of illness classification. A telephone survey was administered to the caregivers of all enrolled patients in the study sample. RESULTS: Four elements of pediatric asthma care were examined: quality, access, hospital utilization, and functional impact of disease. Demographic data were similar between the ED cases and the AC controls. In terms of quality of care, the AC patients were more likely to use maintenance antiinflammatory medications, 60.2% vs 22.5% (OR = 5.3; 95% CI = 2.9 to 9.7) and more likely to be taking medications at school, 71.4% vs 48.1% (OR = 2.7; 95% CI = 1.5 to 4.7). In terms of access to care, the AC families were more likely to have a physician to call to assist with outpatient management, 98.2% vs 65.0% (OR = 25.3; 95% CI = 9.0 to 76.9). Frequent ED utilization (> or = 1 visit/month) was less likely in the AC patients, 9.2% vs 22.0% (OR = 0.35; 95% CI = 0.16 to 0.79) and school absenteeism was lower as well (9.5 +/- 6.7 days vs 16.6 +/- 10.3, p < 0.001). Additionally, the caregivers of the AC patients missed fewer workdays (4.7 +/- 2.8 vs 7.4 +/- 4.1; p = 0.03). CONCLUSIONS: Significant disparities in quality, access, resource utilization, and functional impact exist between AC and ED patients. Emergency physicians have a unique opportunity to improve the public health by directing ED patients toward pediatric AC treatment.

Gender differences in utilization of exercise treadmill testing: a claims-based analysis.

Significant data exist to suggest that women with coronary artery disease (CAD) have worse outcomes than men. One explanation is that women present with more advanced disease because of a lack of screening and early detection. To examine this, we performed a claims-based analysis of exercise treadmill testing (ETT) within an urban managed care population. We analyzed all claims for 57,793 covered lives. Utilization rates for ETT were calculated for men and women by age group. ETT utilization between men and women demonstrated significant differences: 49.2 tests/1,000 men versus 25.0 tests/1,000 women (p < 0.001). This 2:1 ratio was observed across multiple age strata. Significant differences in ETT utilization exist between men and women, even in older populations in which the incidence of CAD in women exceeds that in men. ETT often is the initial screening test for detecting CAD; these gender differences in ETT utilization may result in underdetection of CAD in women and treatment at later stages of disease when interventions are less effective.

Reduction in angioplasty complications after the introduction of coronary stents: results from a consecutive series of 2242 patients.

The introduction of coronary stents for the treatment of acute vessel closure has probably improved the safety of angioplasty, but little data are available regarding angioplasty complication rates when bailout stenting is available. Therefore baseline and patient outcome data for 2242 consecutive patients treated at a single tertiary referral center were compared before and after bailout coronary stenting was introduced. Patients treated after stents became available were more likely to have diabetes (16% prestent availability vs 19% poststent, p < 0.05), unstable angina (61% prestent vs 70% poststent, p < 0.01), and to have received intravenous nitroglycerin before the procedure (22% prestent vs 28% poststent, p < 0.01). Major complications occurred in 4.1% of patients before stent availability and 2.0% afterwards (p < 0.01). These complications included in-hospital death (1.1% prestent vs 0.7% poststent, p = not significant [NS]), Q wave myocardial infarction (0.5% prestent vs 0.3% poststent, p = NS), and emergency bypass surgery (2.9% prestent vs 1.1% poststent, p < 0.01). The introduction of coronary stents was associated with a > 50% reduction in major complications despite greater patient acuity. The traditionally reported complication rates for angioplasty appear not to apply when ballout stenting is available.

Intracoronary stents.

Interventional cardiology has undergone exciting changes since the first percutaneous transluminal coro-_ nary angioplasty was performed by Andreas Gruentzig in 1977.' Over the last several years, a variety of techniques have been developed which provide the interventional cardiologist with a range of options to treat coronary stenoses. In addition, the indications for intervention have radically changed since the original work by Gruentzig, who limited treatment to patients with a single focal stenosis in a large vessel. Advances in balloon angioplasty, as well as the development of new techniques such as directional atherectomy, laser angioplasty, rotational atherectomy, extraction atherectomy, and now intracoronary stents have given the interventional cardiologist the ability to treat multivessel disease, increasingly complex lesions, and less stable patients."

Mechanism of repetitive monomorphic ventricular tachycardia.

BACKGROUND: The most common form of idiopathic ventricular tachycardia (VT) is repetitive monomorphic VT (RMVT), which is characterized by frequent ventricular ectopy and salvos of nonsustained VT with intervening sinus rhythm. Unlike most other forms of idiopathic VT, this tachycardia typically occurs at rest and is nonsustained. The mechanism of RMVT is undefined. Because of a common site of origin, the right ventricular outflow tract (RVOT), we hypothesized that RMVT is mechanistically related to paroxysmal sustained, exercise-induced VT, which has been shown to be consistent with cAMP-mediated triggered activity. Therefore, in this study, we sought to identify (1) the mechanism of RMVT at the cellular level by using electropharmacological probes known to activate either stimulatory or inhibitory G proteins and thereby modify intracellular cAMP levels, (2) potential autonomic triggers of RMVT through analysis of heart rate variability, and (3) whether well-characterized somatic activating mutations in the stimulatory G protein, G alpha s, underlie RMVT. METHODS AND RESULTS: Twelve patients with RMVT underwent electrophysiological study. Sustained monomorphic VT was reproducibly initiated and terminated with programmed stimulation and/or isoproterenol infusion in 11 of the 12 patients (the other patient had incessant RMVT). Induction of VT demonstrated cycle length dependence and was facilitated by rapid atrial or ventricular pacing. Termination of VT occurred in response to interventions that either lowered stimulated levels of intracellular cAMP (and thus decreased intracellular Ca2+)--ie, adenosine (12 of 12), vagal maneuvers or edrophonium (8 of 9), and beta-blockade (3 of 5)--or directly decreased the slow-inward calcium current--ie, verapamil (10 of 12). Analysis of heart rate variability during 24-hour ambulatory monitoring in 7 patients showed that the sinus heart rate is increased and accelerates before nonsustained VT (P < .05), whereas high-frequency heart rate variability is unchanged. These findings are consistent with transient increases in sympathetic tone preceding nonsustained VT. Finally, myocardial biopsy samples were obtained from the site of origin of the VT (typically the RVOT) and from the right ventricular apex from 9 patients. Genomic DNA was extracted from each biopsy sample, and three exons of G alpha s in which activating mutations have previously been described were amplified by polymerase chain reaction. All sequences from these regions were found to be identical to that of control. CONCLUSIONS: Although the arrhythmia occurs at rest, the constellation of findings in idiopathic VT that is characterized by RMVT is consistent with the mechanism of cAMP-mediated triggered activity. Therefore, the spectrum of VT resulting from this mechanism includes not only paroxysmal exercise-induced VT but also RMVT.

HSV-1 vector-mediated gene transfer of the human nerve growth factor receptor p75hNGFR defines high-affinity NGF binding.

A series of recombinant herpes simplex virus (HSV-1) vectors have been constructed that encode either the full-length cDNA of the human p75 NGF receptor (p75hNGFR) or truncated forms of the receptor. Infection of cultured fibroblast cells with viral stocks results in abundant expression of all three cDNAs, as detected by affinity cross-linking, immunoblot analysis, and equilibrium binding. Furthermore, viral infection of primary neuronal cultures gives easily detectable p75 expression by immunofluorescence and affinity cross-linking. When p75 was introduced by viral infection into fibroblast cells expressing the trk proto-oncogene, a new binding site was created, consistent with high-affinity NGF binding. This site is not created by the coexpression of truncated forms of p75 that lack either the extracellular ligand binding domain or the cytoplasmic domain of the receptor, suggesting that both of these regions of the receptor are required for the formation of the high-affinity NGF binding site. Hence, these HSV-1 vectors give rise to appropriate NGF receptor binding after viral infection. The application of these HSV-1 constructs to primary neuronal culture and in vivo models of p75NGFR function is discussed.