Use of recombinant activated factor VII for acute bleeding episodes in acquired hemophilia: final analysis from the Hemostasis and Thrombosis Research Society Registry acquired hemophilia study

The Hemostasis and Thrombosis Research Society Registry was used to monitor the postapproval use and safety of recombinant activated factor VII (rFVIIa). The objective of this article is to evaluate the data from the Hemostasis and Thrombosis Research Society Registry related to rFVIIa-treated bleeding episodes in patients with acquired hemophilia. For each rFVIIa-treated bleeding episode, the initial dose, total dose, average infused dose, number of doses, and treatment duration were calculated. Efficacy was assessed on a three-point scale. Out of the 166 registered patients with acquired hemophilia, 110 patients were treated for 237 bleeding episodes (139 rFVIIa treated); the majority (70%) were in patients older than 60 years. The most frequently reported bleeding locations were subcutaneous (40%) and mucosal (32%). Subcutaneous bleeding episodes were more commonly reported in women (55% vs. 40% men) and white patients (44 vs. 27% black). Of the 139 rFVIIa-treated bleeding episodes, rFVIIa was used as first-line treatment in 127 bleeding episodes. The median initial dose was 90 μg/kg; the median total dose per episode was 333.5 μg/kg. Physician-rated efficacy of rFVIIa for each bleeding episode was reported as ‘bleeding stopped’ in 85% of bleeding episodes, ‘bleeding slowed’ in 11% of bleeding episodes, ‘no improvement’ in 4% of bleeding episodes, and was not documented in 1 bleeding episode. One thromboembolic event was reported; transient neurologic symptoms were reported in a 31-year-old postpartum patient after 110 doses of rFVIIa. Adequate hemostasis was provided for most rFVIIa-treated bleeding episodes at doses largely conforming to the package insert. No major safety concerns were reported

Consensus recommendations for the diagnosis and treatment of acquired hemophilia A

<p>Abstract</p> <p>Background</p> <p>Acquired hemophilia A (AHA) is a rare bleeding disorder caused by an autoantibody to coagulation factor (F) VIII. It is characterized by soft tissue bleeding in patients without a personal or family history of bleeding. Bleeding is variable, ranging from acute, life-threatening hemorrhage, with 9-22% mortality, to mild bleeding that requires no treatment. AHA usually presents to clinicians without prior experience of the disease, therefore diagnosis is frequently delayed and bleeds under treated.</p> <p>Methods</p> <p>Structured literature searches were used to support expert opinion in the development of recommendations for the management of patients with AHA.</p> <p>Results</p> <p>Immediate consultation with a hemophilia center experienced in the management of inhibitors is essential to ensure accurate diagnosis and appropriate treatment. The laboratory finding of prolonged activated partial thromboplastin time with normal prothrombin time is typical of AHA, and the diagnosis should be considered even in the absence of bleeding. The FVIII level and autoantibody titer are not reliable predictors of bleeding risk or response to treatment. Most patients with AHA are elderly; comorbidities and underlying conditions found in 50% of patients often influence the clinical picture. Initial treatment involves the control of acute bleeding with bypassing agents. Immunosuppressive treatment to eradicate the FVIII inhibitor should be started as soon as the diagnosis is confirmed to reduce the time the patient is at risk of bleeding.</p> <p>Conclusions</p> <p>These recommendations aim to increase awareness of this disorder among clinicians in a wide range of specialties and provide practical advice on diagnosis and treatment.</p

Salinity and temperature balances at the SPURS central mooring during fall and winter

Author Posting. © The Oceanography Society, 2015. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 28, no. 1 (2015): 56-65, doi:10.5670/oceanog.2015.06.One part of the Salinity Processes in the Upper-ocean Regional Study (SPURS) field campaign focused on understanding the physical processes affecting the evolution of upper-ocean salinity in the region of climatological maximum sea surface salinity in the subtropical North Atlantic (SPURS-1). An upper-ocean salinity budget provides a useful framework for increasing this understanding. The SPURS-1 program included a central heavily instrumented mooring for making accurate measurements of air-sea surface fluxes, as well as other moorings, Argo floats, and gliders that together formed a dense observational array. Data from this array are used to estimate terms in the upper-ocean salinity and heat budgets during the SPURS-1 campaign, with a focus on the first several months (October 2012 to February 2013) when the surface mixed layer was becoming deeper, fresher, and cooler. Specifically, we examine the salinity and temperature balances for an upper-ocean mixed layer, defined as the layer where the density is within 0.4 kg m–3 of its surface value. The gross features of the evolution of upper-ocean salinity and temperature during this fall/winter season are explained by a combination of evaporation and precipitation at the sea surface, horizontal transport of heat and salt by mixed-layer currents, and vertical entrainment of fresher, cooler fluid into the layer as it deepened. While all of these processes were important in the observed seasonal (fall) freshening at this location in the salinity-maximum region, the variability of salinity on monthly-to-intraseasonal time scales resulted primarily from horizontal advection.J.T. Farrar, A.J. Plueddemann, J.B. Edson, and the deployment of the central mooring were supported by NASA grant NNX11AE84G. L. Rainville, C. Lee, C. Eriksen, and the Seaglider program were supported by NASA grant NNX11AE78G. R. Schmitt was supported by NSF grant OCE-1129646. B. Hodges and D. Fratantoni were supported by NASA grant NNX11AE82G. The Prawler moorings were funded by PMEL. The data analysis was also supported by NASA grant NNX14AH38G

Single or Double Degenerate Progenitors? Searching for Shock Emission in the SDSS-II Type Ia Supernovae

From the set of nearly 500 spectroscopically confirmed type~Ia supernovae and around 10,000 unconfirmed candidates from SDSS-II, we select a subset of 108 confirmed SNe Ia with well-observed early-time light curves to search for signatures from shock interaction of the supernova with a companion star. No evidence for shock emission is seen; however, the cadence and photometric noise could hide a weak shock signal. We simulate shocked light curves using SN Ia templates and a simple, Gaussian shock model to emulate the noise properties of the SDSS-II sample and estimate the detectability of the shock interaction signal as a function of shock amplitude, shock width, and shock fraction. We find no direct evidence for shock interaction in the rest-frame $B$-band, but place an upper limit on the shock amplitude at 9% of supernova peak flux ($M_B > -16.6$ mag). If the single degenerate channel dominates type~Ia progenitors, this result constrains the companion stars to be less than about 6 $M_{\odot}$ on the main sequence, and strongly disfavors red giant companions.Comment: 28 pages, 3 figure

Assessment of acquired hemophilia patient demographics in the United States: the Hemostasis and Thrombosis Research Society Registry

The Hemostasis and Thrombosis Research Society (HTRS) Registry was used to monitor the postapproval use of recombinant factor VIIa. The objective of this manuscript is to provide key insights on the demographics of patients with acquired hemophilia in the HTRS Registry. Acquired hemophilia patient registration in HTRS captured age; sex; comorbidities and predisposing conditions; first bleeding location; laboratory parameters; exposure to blood products, factor, and bypassing agents; and initiation of immune suppression/tolerance therapy. Overall, 166 patients with acquired hemophilia were registered in HTRS (83 women, 73 men, median age 70 years); the majority were non-Hispanic whites (61.4%). The most common comorbidities were autoimmune disease (28.4%) and malignancy (14.5%). The most common first site of bleeding was subcutaneous (27.1%); this was more common in whites (29.1%) than blacks (12.5%) and in non-Hispanics (26.4%) than Hispanics (11.8%). Blood product exposure was reported for 33.1% of patients; the most commonly reported product was packed red blood cells (28%). Of the 57 patients with outcome data available for immune tolerance therapy, 26 patients (46%) reported successful treatment, 13 reported unsuccessful treatment (23%), and 18 (32%) were receiving active treatment at the time of registration. The HTRS Registry final analysis provides the only current comprehensive look at acquired hemophilia in the US population, including details on underlying autoimmune diseases and malignancies. Pertinent to recognition and diagnosis of the disease, subcutaneous bleeding as a presenting bleeding symptom was more common in white and non-Hispanic individuals

Phenotypic Expressions of CCR5-Δ32/Δ32 Homozygosity

Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Δ32/Δ32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-Δ32/Δ32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-Δ32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. Results: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-Δ32/Δ32 study subjects. Based on blood pressure measurement and treatment history, CCR5-Δ32/Δ32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were ~20% higher in CCR5-Δ32/Δ32 study subjects than in CCR5-+/+ study subjects (p \u3c .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-Δ32/Δ32 homozygotes (p \u3c .05), but serum HCV levels did not differ by CCR5-Δ32 genotype. CCR5-Δ32/Δ32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. Conclusions: CCR5-Δ32/Δ32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-Δ32/Δ32 homozygosity does not provide broad protection against viral infections

The Subluminous Supernova 2007qd: A Missing Link in a Family of Low-Luminosity Type Ia Supernovae

We present multi-band photometry and multi-epoch spectroscopy of the peculiar Type Ia supernova (SN Ia) 2007qd, discovered by the SDSS-II Supernova Survey. It possesses physical properties intermediate to those of the peculiar SN 2002cx and the extremely low-luminosity SN 2008ha. Optical photometry indicates that it had an extraordinarily fast rise time of <= 10 days and a peak absolute B magnitude of -15.4 +/- 0.2 at most, making it one of the most subluminous SN Ia ever observed. Follow-up spectroscopy of SN 2007qd near maximum brightness unambiguously shows the presence of intermediate-mass elements which are likely caused by carbon/oxygen nuclear burning. Near maximum brightness, SN 2007qd had a photospheric velocity of only 2800 km/s, similar to that of SN 2008ha but about 4000 and 7000 km/s less than that of SN 2002cx and normal SN Ia, respectively. We show that the peak luminosities of SN 2002cx-like objects are highly correlated with both their light-curve stretch and photospheric velocities. Its strong apparent connection to other SN 2002cx-like events suggests that SN 2007qd is also a pure deflagration of a white dwarf, although other mechanisms cannot be ruled out. It may be a critical link between SN 2008ha and the other members of the SN 2002cx-like class of objects.Comment: To be published in the Astrophysical Journal; 37 pages, 13 figures, 4 table

Inverse plan optimization accounting for random geometric uncertainties with a multiple instance geometry approximation (MIGA)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135142/1/mp1016.pd

Autonomous multi-platform observations during the Salinity Processes in the Upper-ocean Regional Study

Author Posting. © The Oceanography Society, 2017. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 30, no. 2 (2017): 38–48, doi:10.5670/oceanog.2017.218.The Salinity Processes in the Upper-ocean Regional Study (SPURS) aims to understand the patterns and variability of sea surface salinity. In order to capture the wide range of spatial and temporal scales associated with processes controlling salinity in the upper ocean, research vessels delivered autonomous instruments to remote sites, one in the North Atlantic and one in the Eastern Pacific. Instruments sampled for one complete annual cycle at each of these two sites, which are subject to contrasting atmospheric forcing. The SPURS field programs coordinated sampling from many different platforms, using a mix of Lagrangian and Eulerian approaches. This article discusses the motivations, implementation, and first results of the SPURS-1 and SPURS-2 programs.SPURS is supported by multiple NASA grants, with important additional contributions from the US National Science Foundation, NOAA, and the Office of Naval Research, as well as international agencies. SVP drifters are deployed with support from NASA and the NOAA funded Global Drifter Program at the Lagrangian Drifter Laboratory of the Scripps Institution of Oceanography. SVP-S2 drifters are provided by NOAA-AOML and NASA. PRAWLER mooring development is supported by NOAA’s Office of Oceanic and Atmospheric Research, Ocean Observing and Monitoring Division, and by NOAA/PMEL