b b-thalassemias are characterized by an imbalance of globin chains with an excess of a-chains which precipitates in erythroid precursors and red blood cells (RBCs) leading to inefficient erythropoiesis. The severity of the disease correlates with the amount of unpaired achains. Our goal was to develop a simple test for evaluation of the free a-hemoglobin pool present in RBC lysates. Alpha-Hemoglobin Stabilizing Protein (AHSP), the chaperone of a-Hb, was used to trap excess aHb. A recombinant GST-AHSP fusion protein was bound to an affinity micro-column and then incubated with hemolysates of patients. After washing, the a-Hb was quantified by spectrophotometry in the elution fraction. This assay was applied to 54 patients: 28 without apparent Hb disorder, 20 b-thalassemic and 6 a-thalassemic. The average value of free a-Hb pool was 93 ± 21 ppm (ng of free a-Hb per mg of Hb subunits) in patients without Hb disorder, while it varies from 119 to 1,756 ppm, in b-thalassemic patients and correlated with genotype. In contrast, the value of the free a-Hb pool was decreased in a-thalassemic patients (65 ± 26 ppm). This assay may help to characterize b-thalassemia phenotypes and to follow the evolution of the globin chain imbalance (a/b+c ratio) in response to treatment.b-thalassemias (b-thal) are inherited autosomal diseases characterized by a decreased or abolished b-globin chain biosynthesis [1]. During the transition of g to b globin expression in the first year of life, the clinical severity is mainly related to the ratio a/b1g which indicates the level of chain disequilibrium. b-thal are generally classified as minor, intermediate, or major phenotype, and encompass a wide clinical spectrum ranging from asymptomatic carriers to forms that can be lethal in the absence of extensive treatment. Different factors can modulate the severity of this disease [2] such as the magnitude of the decrease of the b globin synthesis, for example hemoglobin E (Hb E b26Glu?Lys) [3], or with the co-inheritance of (i) an a-thalassemia (a-thal) [4], (ii) a triplicated a-globin gene [5] or (iii) a low but variable residual capacity of g globin production which can have the phenotype of a hereditary persistence of fetal Hb (Hb F a 2 g 2 ) [6].The imbalance between a and non a-globin (g1d1b) synthesis was established by radioactive in vitro biosynthesis of globin chains from reticulocytes or of bone marrow of b-thalassemic patients [7][8][9][10]. This imbalance leads to an excess of highly unstable free a-hemoglobin (a-Hb), precipitating on the cell membrane and acting as active oxidants causing apoptosis and inefficient erythropoiesis [1,11]. The severity of b-thal is directly correlated with the degree of imbalance as quantified by the amount of unbound a-globin chain [12]. Many studies have shown that one observes a soluble a chain fraction present in the cytosolic RBC and an insoluble a chain fraction in the membrane of b-thalassemic erythrocytes [13,14]. Because of technical difficulties and the burden of using radioactive materials, ...

Objective. Healthcare utilization and costs associated with systemic lupus erythematosus (SLE) in a US Medicaid population were examined. Methods. Patients ≥ 18 years old with SLE diagnosis (ICD-9-CM 710.0x) were extracted from a large Medicaid database 2002–2009. Index date was date of the first SLE diagnosis. Patients with and without SLE were matched. All patients had a variable length of followup with a minimum of 12 months. Annualized healthcare utilization and costs associated with SLE and costs of SLE flares were assessed during the followup period. Multivariate regressions were conducted to estimate incremental healthcare utilization and costs associated with SLE. Results. A total of 14,777 SLE patients met the study criteria, and 14,262 were matched to non-SLE patients. SLE patients had significantly higher healthcare utilization per year than their matched controls. The estimated incremental annual cost associated with SLE was $10,984, with the highest increase in inpatient costs (P < 0.001). Cost per flare was $11,716 for severe flares, $562 for moderate flares, and $129 for mild flares. Annual total costs for patients with severe flares were $49,754. Conclusions. SLE patients had significantly higher healthcare resource utilization and costs than non-SLE patients. Patients with severe flares had the highest costs.

BackgroundHerpes zoster (HZ), also known as shingles, is a painful and commonly occurring condition in the United States. In spite of a universally recommended vaccine for use in immunocompetent adults aged 60 years and older, HZ continues to impact the American public, and a better understanding of its current incidence is needed. The objective of the current study is to estimate the overall and age- and gender-specific incidence rates (IRs) of HZ among an immunocompetent US population in 2011 following availability of a vaccine.MethodsClaims data from the Truven Health MarketScan® Research databases between 01/01/2011 and 12/31/2011 were extracted. Immunocompetent adult patients, enrolled as of January 1, 2011 were analyzed. The denominator was defined as eligible subjects who were immunocompetent, had no evidence of zoster vaccination, and no diagnosis of HZ (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 053.xx) in the 90 days prior to January 1, 2011. Subjects contributed person-days to the denominator until the occurrence of one of the following events: end of continuous enrollment in the database, a claim for zoster vaccination, diagnosis of HZ or end of the observation period (December 31, 2011). The numerator was defined as enrollees within the denominator file exhibiting evidence of HZ. Annual IRs were calculated for the entire population in the database as well as by gender and age group; standardized IRs were also produced using the 2010 US Census data.ResultsThe overall annual IR of HZ across all ages was 4.47 per 1000 person-years (95 % confidence interval [CI]: 4.44–4.50) which monotonically increased with age from 0.86 (95 % CI: 0.84–0.88) for those aged ≤19 to 12.78 (95 % CI: 12.49–13.07) for patients ≥80 years. The IR was 8.46 (95 % CI: 8.39–8.52) among adults ≥50 years and 10.46 (95 % CI: 10.35–10.56) among those aged ≥60 years. Women compared to men had higher HZ incidence (5.25, 95 % CI: 5.21–5.29 vs. 3.66, 95 % CI: 3.62–3.69) and this was seen across all age groups. When adjusted for age and gender using 2010 US Census data, the annual IR was 4.63 per 1000 person-years (95 % CI: 4.61–4.66).ConclusionsDespite the availability of a vaccine, HZ remains common among immunocompetent adults in the US with incidence rates of HZ observed to increase with age and be higher in women than men.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1262-8) contains supplementary material, which is available to authorized users.

ObjectivesThe mean lifetime cost of ischemic stroke is approximately $140,048 in the United States, placing stroke among the top 10 most costly conditions among Medicare beneficiaries. The objective of this study was to describe the health-care resource utilization and costs in the year following hospitalization for acute ischemic stroke (AIS).MethodsThis retrospective claims analysis quantifies utilization and costs following inpatient admission for AIS among the commercially insured and Medicare beneficiaries in the Truven Health databases. Patients who were 18 years or older and continuously enrolled for 12 months before and after an AIS event occurring (index) between January 2009 and December 2012 were identified. Patients with AIS in the year preindex were excluded. Demographic and clinical characteristics were evaluated at admission and in the preindex, respectively. Direct costs, readmissions, and inpatient length of stay (LOS) were described in the year postindex.ResultsThe eligible populations comprised 20,314 commercially insured patients and 31,037 Medicare beneficiaries. Average all-cause costs were $61,354 and $44,929 (commercial and Medicare, respectively) in the first year after the AIS. Approximately 50%–55% of total 12-month costs were incurred between day 31 and day 365 following the incident AIS. One quarter (24.6%) of commercially insured patients and 38.8% of Medicare beneficiaries were readmitted within 30 days with 16.6% and 71.7% (commercial and Medicare, respectively) of those having a principal diagnosis of AIS. The average AIS-related readmission length of stay was nearly three times that of the initial hospitalization for both commercially insured patients (3.8 vs 10.8 days) and Medicare beneficiaries (4.0 vs 10.8 days).ConclusionIn addition to the substantial costs of the initial hospitalization of an AIS, these costs double within the year following this event. Given the high cost associated with AIS, new interventions reducing either the acute or longer-term burden of AIS are needed.

Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings. (Study of Perfusion and Anatomy's Role in Coronary Artery [CAD] [SPARC]; NCT00321399).

The Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in CAD (SPARC) is a prospective, multicenter, observational registry that has enrolled 3019 patients undergoing clinically referred SPECT, PET, and CTA with the goal of comparing posttest resource utilization and comparative prognostic value. Resource utilization assessment will enroll intermediate-high likelihood patients without prior CAD, while prognostic assessment will include both these patients and patients with prior CAD. Secondary analyses include assessments of diagnostic accuracy, cost, and referral to revascularization. Sites recruited into at least two of the three imaging arms. Except for semi-quantitative interpretation, site protocols will be used for all imaging studies and images forwarded to an image repository. Follow-up for catheterization, revascularization, cardiac death, myocardial infarction, all-cause death and medication use changes will be performed at 90-day, 1, and 2 years. Standard statistical methods will be used to risk-adjust results within and between study arms. SPARC will have >85% power (two-sided test, alpha = 0.01) to detect a 5% catheterization rate difference at 90 days between the three arms and >90% power to detect a 2% difference in cardiac death, or nonfatal MI within 2 years of the index test.

Background: This study examined real-world etanercept and adalimumab treatment patterns in patients with psoriasis, psoriatic arthritis, or both.Methods:This retrospective analysis utilized data from patients with psoriasis, psoriatic arthritis, or both from a large, US claims database. Outcome measures included persistence on index therapy; pauses (7–59 days) and gaps (≥60 days) in therapy; and rates of discontinuing, switching and restarting index therapy in nonpersistent patients.Results:Of 4,453 patients, 2,534 initiated etanercept and 1,919 initiated adalimumab. In psoriasis patients (n = 2,775), 46.4% and 56.8% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 49.0% and 56.3% discontinued, 23.8% and 22.4% restarted and 14.9% and 11.3% switched index therapy within 12 months. In psoriatic arthritis patients (n = 1,197), 60.7% and 63.3% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 48.3% and 51.6% discontinued, 25.8% and 20.0% restarted and 16.5% and 17.9% switched index therapy. In patients with both (n = 481), 58.1% and 59.6% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 42.7% and 63.2% discontinued, 24.3% and 12.6% restarted and 21.4% and 15.8% switched index therapy.Conclusions:Treatment modifications were common in patients with psoriasis, psoriatic arthritis, or both within 12 months of initiating etanercept or adalimumab.

BackgroundThe goal of this research was to compare the demographics, clinical characteristics and treatment patterns for newly diagnosed multiple sclerosis (MS) patients in a commercial managed care population who received disease-modifying drug (DMD) therapy versus those not receiving DMD therapy.MethodsA retrospective cohort study using US administrative healthcare claims identified individuals newly diagnosed with MS (no prior MS diagnosis 12 months prior using ICD-9-CM 340) and ≥ 18 years old during 2001-2007 to characterize them based on demographics, clinical characteristics, and pharmacologic therapy for one year prior to and a minimum of one year post-index. The index date was the first MS diagnosis occurring in the study period. Follow-up of subjects was done by ICD-9-CM code identification and not by actual chart review. Multivariate analyses were conducted to adjust for confounding variables.ResultsPatients were followed for an average of 35.7 ± 17.5 months after their index diagnosis. Forty-three percent (n = 4,462) of incident patients received treatment with at least one of the DMDs during the post-index period. Treated patients were primarily in the younger age categories of 18-44 years of age, with DMD therapy initiated an average of 5.3 ± 9.1 months after the index diagnosis. Once treatment was initiated, 27.7% discontinued DMD therapy after an average of 17.6 ± 14.6 months, and 16.5% had treatment gaps in excess of 60 days.ConclusionsNearly 60% of newly-diagnosed MS patients in this commercial managed care population remained untreated while over a quarter of treated patients stopped therapy and one-sixth experienced treatment gaps despite the risk of disease progression or a return of pre-treatment disease activity.