Combined prednisolone and intravenous immunoglobulin treatment for acquired factor VIII inhibitors: a 2-year review

Acquired inhibitors to factor VIII (FVIII) are rare, but life- threatening in up to 22% of cases. The optimal therapy for suppression of these inhibitors remains unclear. Prednisolone is the mainstay of therapy, producing responses in approximately 30% of cases. Intravenous immunoglobulin (IVIg) has a similar response rate, but a more rapid effect. We report the results of prednisolone 1 mg kg(-1) combined with IVIg 2 g kg(-1) in divided doses as first-line therapy in seven consecutive patients with acquired FVIII inhibitors. All patients were bleeding at the time of diagnosis with prolonged activated partial thromboplastin time. There were four complete responses, one partial response, one nonresponse and one with an inadequate follow-up for assessment of response, giving an overall response rate of 71%. In all complete responders the inhibitor declined rapidly and was undetectable by day 21 from start of treatment. Therapy was well tolerated and responses have been maintained off treatment for 2-8 months. This is a safe, well-tolerated rapidly acting regimen with good response rates

Risk of recurrence after a first unprovoked venous thromboembolism : external validation of the Vienna Prediction Model with pooled individual patient data

Background: In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. Objective: To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. Patients/Methods: Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. Results: The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P\ua0=\ua00.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12\ua0months. Conclusions: By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence

Analysis of the Physician Variable in Pain Management

The role of physician variability in pain management is unknown. Objective.  To assess the role of physician variability in the management of pain and provide quantitative data regarding the status of pain management in Michigan. Design.  A multi-item mail survey was used to determine the physician's perceived knowledge of pain management modalities, goals, satisfaction, and confidence with pain treatment. Participants. The focus of this report was a group of 368 licensed Michigan physicians who provide clinical care. Results.  Overall, 30% of the study group reported no formal education in pain management, although younger physicians reported more education (correlation coefficient = −0.252, P < .001). The physicians reported greater confidence in their knowledge of meperidine than other Schedule II opioids ( P < .001 ). In regards to the opinion that prescribing strong opioids would attract a medical review, the physician responses ranged from 1 (strongly disagree) to 5 (strongly agree). The median score for this scale was 4, accounting for 46% of the responses. The study group expressed less satisfaction with their treatment of chronic pain as well as lower goals for relief (mean: 3.8; 95% confidence interval: 3.7–3.9). Conclusions.  Lower expectations for relief and less satisfaction in its management may contribute to the undertreatment of chronic pain. Perceptions of regulatory scrutiny may contribute to suboptimal pain management. These preliminary data highlight physician variability in pain decision making while providing insights into educational needs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74700/1/j.1526-4637.2001.01045.x.pd

Networking and the development of professionals: Beginning teachers building social capital

Beginning teachers need support when starting their teaching career. Networking can help teachers develop social capital which supports their development as professionals on their career journey. This paper presents case studies of three secondary school trainee teachers during an English year-long initial teacher education programme. The relationships supporting trainees were characterised differently: for practice development as opposed to enhancing a sense of belonging to the profession. Whether supportive relationships developed depended not only on the trainees but also on others. The paper encourages those involved in teacher education to promote social-capital building as supportive of the development of teachers as professionals

United States Value Set for the Functional Assessment of Cancer Therapy-General Eight Dimensions (FACT-8D), a Cancer-Specific Preference-Based Quality of Life Instrument

Objectives: To develop a value set reflecting the United States (US) general population’s preferences for health states described by the Functional Assessment of Cancer Therapy (FACT) eight-dimensions preference-based multi-attribute utility instrument (FACT-8D), derived from the FACT-General cancer-specific health-related quality-of-life (HRQL) questionnaire. Methods: A US online panel was quota-sampled to achieve a general population sample representative by sex, age (≥ 18 years), race and ethnicity. A discrete choice experiment (DCE) was used to value health states. The valuation task involved choosing between pairs of health states (choice-sets) described by varying levels of the FACT-8D HRQL dimensions and survival (life-years). The DCE included 100 choice-sets; each respondent was randomly allocated 16 choice-sets. Data were analysed using conditional logit regression parameterized to fit the quality-adjusted life-year framework, weighted for sociodemographic variables that were non-representative of the US general population. Preference weights were calculated as the ratio of HRQL-level coefficients to the survival coefficient. Results: 2562 panel members opted in, 2462 (96%) completed at least one choice-set and 2357 (92%) completed 16 choice-sets. Pain and nausea were associated with the largest utility weights, work and sleep had more moderate utility weights, and sadness, worry and support had the smallest utility weights. Within dimensions, more severe HRQL levels were generally associated with larger weights. A preference-weighting algorithm to estimate US utilities from responses to the FACT-General questionnaire was generated. The worst health state’s value was −0.33. Conclusions: This value set provides US population utilities for health states defined by the FACT-8D for use in evaluating oncology treatments

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available