The Economic Burden of Ischemic Stroke and Major Hemorrhage in Medicare Beneficiaries with Nonvalvular Atrial Fibrillation: A Retrospective Claims Analysis

Background

Understanding the economic implications of oral anticoagulation therapy requires careful consideration of the risks and costs of stroke and major hemorrhage. The majority of patients with atrial fibrillation (AF) are aged ≥65 years, so focusing on the Medicare population is reasonable when discussing the risk for stroke.

Objective

To examine the relative economic burden associated with stroke and major hemorrhage among Medicare beneficiaries who are newly diagnosed with nonvalvular atrial fibrillation (NVAF).

Methods

This study was a retrospective analysis of a 5% sample of Medicare claims data for patients with NVAF from 2006 to 2008. Patients with NVAF without any claims of AF during the 12 months before the first (index) claim for AF in 2007 (baseline period) were identified and were classified into 4 cohorts during a 12-month follow-up period after the index date. These cohorts included (1) no claims for ischemic stroke or major hemorrhage (without stroke or hemorrhage); (2) no claims for ischemic stroke and ≥1 claims for major hemorrhage (hemorrhage only); (3) ≥1 claims for ischemic stroke and no major hemorrhage claims (stroke only); and (4) ≥1 claims each for ischemic stroke and for major hemorrhage (stroke and hemorrhage). The 1-year mean postindex total all-cause healthcare costs adjusted by the Centers for Medicare & Medicaid Services Hierarchical Condition Categories (HCC) score were compared among the study cohorts. Results: Of the 9455 eligible patients included in this study, 3% (N = 261) of the patients had ischemic stroke claims only, 3% (N = 276) had hemorrhage claims only, and <1% (N = 13) had both during the follow-up period. The unadjusted follow-up healthcare costs were $63,781 and $64,596 per patient for the ischemic stroke only and the hemorrhage only cohorts, respectively, compared with $35,474 per patient for those without hemorrhage or stroke claims. After adjustment for HCC risk score, the mean incremental costs for patients with stroke claims only and hemorrhage claims only, relative to those without stroke or hemorrhage claims, were $26,776 (95% confidence interval [CI], $20,785-$32,767; P <.001) and $26,168 (95% CI, $20,375-$31,961; P <.001), respectively.

Conclusion

The economic burden of managing patients with NVAF who experience ischemic stroke and hemorrhage were similarly significant during the first year after a diagnosis of NVAF. The burden of major bleeding complications on patients, clinicians, and payers should not be overlooked, and these complications should be considered in conjunction with the cost-savings associated with ischemic stroke risk reduction in future cost-benefit evaluations of oral anticoagulation therapy.Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia.1,2 The most recent estimates (published in 2013) of the prevalence of AF in the United States are for 2010 and range from 2.7 million to 6.1 million.3,4 The prevalence of AF doubles with each decade of life after the age of 60 years and occurs in approximately 10% of the US population aged ≥80 years.5–7 A recent study estimates that the number of patients with AF in the United States could potentially reach 12.1 million by 20303; other estimates range from 5.6 million to 12 million patients with AF by 2050.4Patients with AF have an approximate 5-fold increased risk for stroke compared with patients in normal sinus rhythm.4 Furthermore, the percentage of strokes that can be attributed to AF increases steeply with age, with rates of 1.5% in patients aged 50 to 59 years and 23.5% in those aged 80 to 89 years.4 The term “nonvalvular atrial fibrillation” (NVAF) is used to describe cases of AF that occur in the absence of rheumatic mitral valve disease, mitral valve repair, or a prosthetic heart valve.8 NVAF affects approximately 85% of the overall population with AF and is a substantial medical burden for Medicare beneficiaries (aged ≥65 years) in the United States.9,10The current evidence-based clinical guidelines recommend the use of oral anticoagulation in patients with NVAF who are at an intermediate to high risk for stroke.8,11 Although the efficacy of oral anticoagulation therapy to prevent stroke in patients with NVAF is well-established, it is also associated with a risk of bleeding.12–15 Understanding the relative economic burdens of stroke and major hemorrhage is important when considering the costs and benefits of anticoagulation therapy.Several studies have reported the incremental costs associated with stroke alone or with hemorrhage alone using different NVAF payer populations (ie, commercial or Medicare), and a few recent studies have provided incremental cost data for stroke and hemorrhage for the Medicare population, reporting significant incremental costs in the year after the stroke or hemorrhage index dates.7,16–20 Other studies have analyzed the incremental costs associated with stroke alone or with hemorrhage alone, or have analyzed these costs for a commercial population with NVAF.21–24 Most of these studies were done in separate patient populations and different time periods, making assessment of the relative economic burden of stroke versus bleeding difficult. By contrast, our study provides the cost estimates for these 2 conditions simultaneously based on the same patient population, which allows a more appropriate comparison of the economic implication of these 2 major consequences of oral anticoagulation therapy for the prevention of stroke among patients with NVAF.The prespecified objective in our study was to assess the relative economic burden (including Medicare Part D costs) associated with ischemic stroke and with major hemorrhagic events (ie, intracranial and gastrointestinal [GI] bleeding) among Medicare beneficiaries with newly diagnosed NVAF in the 12 months after the NVAF index diagnosis.     

Covalent structure of human haptoglobin: a serine protease homolog.

The complete amino acid sequences and the disulfide arrangements of the two chains of human haptoglobin 1-1 were established. The alpha 1 and beta chains of haptoglobin contain 83 and 245 residues, respectively. Comparison of the primary structure of haptoglobin with that of the chymotrypsinogen family of serine proteases revealed a significant degree of chemical similarity. The probability was less than 10(-5) that the chemical similarity of the beta chain of haptoglobin to the proteases was due to chance. The amino acid sequence of the beta chain of haptoglobin is 29--33% identical to bovine trypsin, bovine chymotrypsin, porcine elastase, human thrombin, or human plasmin. Comparison of haptoglobin alpha 1 chain to activation peptide regions of the zymogens revealed an identity of 25% to the fifth "kringle" region of the activation peptide of plasminogen. The probability was less than 0.014 that this similarity was due to chance. These results strongly indicate haptoglobin to be a homolog of the chymotrypsinogen family of serine proteases. Alignment of the beta-chain sequence of haptoglobin to the serine proteases is remarkably consistent except for an insertion of 16 residues in the region corresponding to the methionyl loop of the serine proteases. The active-site residues typical of the serine proteases, histidine-57 and serine-195, are replaced in haptoglobin by lysine and alanine, respectively; however, aspartic acid-102 and the trypsin specificity, residue, aspartic acid-189, do occur in haptoglobin. Haptoglobin and the serine proteases represent a striking example of homologous proteins with different biological functions.     

CHLOROQUINE RESISTANCE IN MALARIA: A DEFICIENCY OF CHLOROQUINE BINDING

Chloroquine-(14)C was used to study the processes which concentrate chloroquine in mouse red blood cells infected with chloroquine-sensitive or with chloroquine-resistant Plasmodium berghei. The initial rates of uptake and exchange of chloroquine-(14)C were both too fast to measure, yet large concentration gradients were maintained by the cells. When red blood cells were exposed to 10(-8)M chloroquine at 22 degrees C, with pH between 7.2 and 7.4, steady-state gradients of chloroquine-(14)C were approximately 600:1 (cells:medium) for cells infected with chloroquine-sensitive parasites, 100:1 for cells comparably infected with chloroquine-resistant parasites, and 14:1 for uninfected cells. The processes responsible for these gradients were saturable, in agreement with the proposal of chloroquine binding to cellular constituents. No degradation of chloroquine was detected.The major difference between the chloroquine-sensitive and -resistant parasites was deficiency of high-affinity binding of chloroquine by cells infected with chloroquine-resistant parasites. This deficiency explains the reduced ability of chloroquine-resistant parasites to concentrate chloroquine, and it suggests that chloroquine resistance is due to a decrease in the number, affinity, or accessibility of chloroquine receptor sites on a constituent of the malaria parasite.     

Medial patellofemoral ligament reconstruction in patellar instability

Background:

Medial patellofemoral ligament (MPFL) is one of the major static medial stabilising structures of the patella. MPFL is most often damaged in patients with patellar instability. Reconstruction of MPFL is becoming a common surgical procedure in treating patellar instability. We hypothesised that MPFL reconstruction was adequate to treat patients with patellar instability if the tibial tubercle and the centre of the trochlear groove (TT-TG) value was less than 20 mm and without a dysplastic trochlea.

Materials and Methods:

30 patients matching our inclusion criteria and operated between April 2009 and May 2011 were included in the study. MPFL reconstruction was performed using gracilis tendon fixed with endobutton on the patellar side and bio absorbable interference screw or staple on the femoral side. Patients were followed up with subjective criteria, Kujala score and Lysholm score.

Results:

The mean duration of followup was 25 months (range 14-38 months). The mean preoperative Kujala score was 47.5 and Lysholm score was 44.7. The mean postoperative Kujala score was 87 and Lysholm score was 88.06. None of the patients had redislocation.

Conclusion:

MPFL reconstruction using gracilis tendon gives excellent results in patients with patellar instability with no redislocations. Some patients may have persistence of apprehension.     

Successful Aortic Valve Replacement Surgery in a Patient with Severe Haemophilia a with Low Titre Inhibitor

Acute leukemia, secondary myelodysplasia and paroxysmal nocturnal hemoglobinuria evolving from severe aplastic anemia (AA) following immunosuppressive therapy are well recognized. However, severe AA occurring after complete remission of acute promyelocytic leukemia (APL) has been documented only once in 2009. We report a case of 30-year-old male diagnosed with APL who achieved complete cytogenetic remission with all-trans retinoic acid based induction regimen and developed severe AA few months later during maintenance therapy.     

Predictors of total and low-density lipoprotein cholesterol change after partial ileal bypass

POSCH is a prospective, randomized secondary intervention trial examining the effect of maximal lipoprotein modification achieved by partial ileal bypass on overall mortality and the course of coronary heart disease. In the initial 189 surgical patients, total cholesterol levels decreased from 256.7 +/- 2.6 mg/dl to 166.6 +/- 2 mg/dl, and low-density lipoprotein cholesterol levels decreased from 181.5 +/- 2.7 mg/dl to 94.1 +/- 1.7 mg/dl 3 months after operation. These significant decreases were sustained through 5 years of follow-up (p less than 0.001). The total cholesterol level was 29.2 +/- 0.9 percent lower and the low-density lipoprotein cholesterol level was 43.2 +/- 1 percent lower at 5 years compared with the baseline level. Decreases of similar magnitude were seen in each of the common WHO lipoprotein phenotypes. The baseline total cholesterol level was the only significant independent preoperative predictor of the 5 year total cholesterol level (correlation coefficient 0.547; p less than 0.001), and the baseline low-density lipoprotein cholesterol level was the only significant independent preoperative determinant of the 5 year low-density lipoprotein cholesterol level (correlation coefficient 0.599; p less than 0.001). These relationships are expressed by the following equations: 5 year total cholesterol = 0.54 X baseline total cholesterol + 42.3, and 5 year low-density lipoprotein cholesterol = 0.455 X baseline low-density lipoprotein cholesterol + 19.2. The decrease in total and low-density lipoprotein cholesterol levels after partial ileal bypass are greater than reported by any trial of drug or diet intervention, including the Lipid Research Clinics Coronary Primary Prevention Trial which examined cholestyramine. Estimation of the change in total and low-density lipoprotein cholesterol levels after partial ileal bypass can be made based on preoperative lipid analysis and is essential in comparing different therapeutic modalities and assessing the role of partial ileal bypass among strategies aimed at lowering coronary heart disease risk.     

Serum protein profile alterations in hemodialysis patients

BACKGROUND: Serum protein profiling patterns can reflect the pathological state of a patient and therefore may be useful for clinical diagnostics. Here, we present results from a pilot study of proteomic expression patterns in hemodialysis patients designed to evaluate the range of serum proteomic alterations in this population. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was used to analyze serum obtained from patients on periodic hemodialysis treatment and healthy controls. Serum samples from patients and controls were first fractionated into six eluants on a strong anion exchange column, followed by application to four array chemistries representing cation exchange, anion exchange, metal affinity and hydrophobic surfaces. A total of 144 SELDI-TOF-MS spectra were obtained from each serum sample. RESULTS: The overall profiles of the patient and control samples were consistent and reproducible. However, 30 well-defined protein differences were observed; 15 proteins were elevated and 15 were decreased in patients compared to controls. Serum from 1 patient exhibited novel protein peaks suggesting possible additional changes due to a secondary disease process. CONCLUSION: SELDI-TOF-MS demonstrated consistent serum protein profile differences between patients and controls. Similarity in protein profiles among dialysis patients suggests that patient physiological responses to end-stage renal disease and/or dialysis therapy have a major effect on serum protein profiles.     

<Emphasis Type="Italic">Hunter disease eClinic:</Emphasis>interactive,computer-assisted,problem-based approach to independent learning about a rare genetic disease

Background  

Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II).     

The Centers for Medicare and Medicaid Services (CMS) Community-Acquired Pneumonia Core Measures Lead to Unnecessary Antibiotic Administration by Emergency Physicians

Objectives: The objectives were to assess emergency physician (EP) understanding of the Centers for Medicare and Medicaid Services (CMS) core measures for community‐acquired pneumonia (CAP) guidelines and to determine their self‐reported effect on antibiotic prescribing patterns. Methods: A convenience sample of EPs from five medical centers in North Carolina was anonymously surveyed via a Web‐based instrument. Participants indicated their level of understanding of the CMS CAP guidelines and the effects on their prescribing patterns for antibiotics. Results: A total of 121 EPs completed the study instrument (81%). All respondents were aware of the CMS CAP guidelines. Of these, 95% (95% confidence interval [CI] = 92% to 98%) correctly understood the time‐based guidelines for antibiotic administration, although 24% (95% CI = 17% to 31%) incorrectly identified the onset of this time period. Nearly all physicians (96%; 95% CI = 93% to 99%) reported institutional commitment to meet these core measures, and 84% (95% CI = 78% to 90%) stated that they had a department‐based CAP protocol. More than half of the respondents (55%; 95% CI = 47% to 70%) reported prescribing antibiotics to patients they did not believe had pneumonia in an effort to comply with the CMS guidelines, and 42% (95% CI = 34% to 50%) of these stated that they did so more than three times per month. Only 40% (95% CI = 32% to 48%) of respondents indicated a belief that the guidelines improve patient care. Of those, this was believed to occur by increasing pneumonia awareness (60%; 95% CI = 52% to 68%) and improving hospital processes when pneumonia is suspected (86%; 95% CI = 80% to 92%). Conclusions: Emergency physicians demonstrate awareness of the current CMS CAP guidelines. Most physicians surveyed reported the presence of institutional protocols to increase compliance. More than half of EPs reported that they feel the guidelines led to unnecessary antibiotic usage for patients who are not suspected to have pneumonia. Only 40% of EPs believe that CAP awareness and expedient care resulting from these guidelines has improved overall pneumonia‐related patient care. Outcome‐based data for non–intensive care unit CAP patients are lacking, and EPs report that they prescribe antibiotics when they may not be necessary to comply with existing guidelines.     

Histogram analysis of MR imaging-derived cerebral blood volume maps： combined glioma grading and identification of low-grade oligodendroglial subtypes

BACKGROUND AND PURPOSE： Inclusion of oligodendroglial tumors may confound the utility of MR based glioma grading. Our aim was, first, to assess retrospectively whether a histogram-analysis method of MR peifusion images may both grade gliomas and differentiate between low-grade oligodendroglial tumors with or without loss of heterozygosity （LOH） on 1p/19q and, second, to assess retrospectively whether low-grade oligodendroglial subtypes can be identified in a population of patients with high-grade and low-grade astrocytic and oligodendroglial tumors.