Summary
Background
Discriminative drug level thresholds for disease activity endpoints in patients with Crohn's disease. have been consistently demonstrated with infliximab, but not adalimumab.
Aims
...To identify threshold concentrations for infliximab and adalimumab in Crohn's disease according to different disease endpoints, and factors that influence drug levels.
Methods
We performed a cross‐sectional service evaluation of patients receiving maintenance infliximab or adalimumab for Crohn's disease. Serum drug levels were at trough for infliximab and at any time point for adalimumab. Endpoints included Harvey‐Bradshaw index, C‐reactive protein and faecal calprotectin. 6‐tioguanine nucleotide (TGN) concentrations were measured in patients treated with thiopurines.
Results
A total of 191 patients (96 infliximab, 95 adalimumab) were included. Differences in infliximab levels were observed for clinical (P=.081) and biochemical remission (P=.003) and faecal calprotectin normalisation (P<.0001) with corresponding thresholds identified on ROC analysis of 1.5, 3.4 and 5.7 μg/mL. Adalimumab levels were similar between active disease and remission regardless of the endpoint assessed. Modelling identified that higher infliximab dose, body mass index and colonic disease independently accounted for 31% of the variation in infliximab levels, and weekly dosing, albumin and weight accounted for 23% of variation in adalimumab levels. TGN levels did not correlate with drug levels.
Conclusions
Infliximab drug levels are associated with the depth of response/remission in patients with Crohn's disease, but no such relationship was observed for adalimumab. More data are needed to explain the variation in drug levels.
Linked ContentThis article is linked to Seow and Panacionne and Ward and Irving papers. To view these articles visit https://doi.org/10.1111/apt.14185 and https://doi.org/10.1111/apt.14209.
Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used ...interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.
Abstract
The Foundation Supernova Survey aims to provide a large, high-fidelity, homogeneous, and precisely calibrated low-redshift Type Ia supernova (SN Ia) sample for cosmology. The calibration of ...the current low-redshift SN sample is the largest component of systematic uncertainties for SN cosmology, and new data are necessary to make progress. We present the motivation, survey design, observation strategy, implementation, and first results for the Foundation Supernova Survey. We are using the Pan-STARRS telescope to obtain photometry for up to 800 SNe Ia at z ≲ 0.1. This strategy has several unique advantages: (1) the Pan-STARRS system is a superbly calibrated telescopic system, (2) Pan-STARRS has observed 3/4 of the sky in grizyP1 making future template observations unnecessary, (3) we have a well-tested data-reduction pipeline, and (4) we have observed ∼3000 high-redshift SNe Ia on this system. Here, we present our initial sample of 225 SN Ia grizP1 light curves, of which 180 pass all criteria for inclusion in a cosmological sample. The Foundation Supernova Survey already contains more cosmologically useful SNe Ia than all other published low-redshift SN Ia samples combined. We expect that the systematic uncertainties for the Foundation Supernova Sample will be two to three times smaller than other low-redshift samples. We find that our cosmologically useful sample has an intrinsic scatter of 0.111 mag, smaller than other low-redshift samples. We perform detailed simulations showing that simply replacing the current low-redshift SN Ia sample with an equally sized Foundation sample will improve the precision on the dark energy equation-of-state parameter by 35 per cent, and the dark energy figure of merit by 72 per cent.
Mechanics of hollow sphere foams Sanders, W.S.; Gibson, L.J.
Materials science & engineering. A, Structural materials : properties, microstructure and processing,
04/2003, Letnik:
347, Številka:
1
Journal Article
Recenzirano
Models for the mechanical properties of foams suggest that closed-cell foams should have significantly higher modulus and strength than open-cell foams, especially at low relative densities. In ...practice, as a result of defects in their microstructure, the measured properties of closed-cell metallic foams are similar to those of open-cell foams of the same relative density. Hollow sphere foams provide an alternative microstructure with the potential for improved properties for low-density metal structures. Here, we analyze the elastic moduli and initial yield strength of hollow sphere foams. The results indicate that their theoretical values of moduli and strength are intermediate to those for open- and closed-cell foams. With suitable manufacturing techniques, hollow sphere foams have the potential for improved mechanical properties compared with existing metallic foams.
Using broad interrogation of clinically relevant drug absorption, distribution, metabolism, and excretion (ADME) genes on the DMET platform, we identified a genetic variant in SLCO1B1 (rs2291075; ...c.597C>T), encoding the transporter OATP1B1, associated with event‐free (P = 0.006, hazard ratio = 1.74) and overall survival (P = 0.012, hazard ratio = 1.85) in children with de novo acute myeloid leukemia (AML). Lack of SLCO1B1 expression in leukemic blasts suggested the association might be due to an inherited rather than a somatic effect. rs2291075 was in strong linkage with known functional variants rs2306283 (c.388A>G) and rs4149056 (c.521T>C). Functional studies in vitro determined that four AML‐directed chemotherapeutics (cytarabine, daunorubicin, etoposide, and mitoxantrone) are substrates for OATP1B1 and the mouse ortholog Oatp1b2. In vivo pharmacokinetic studies using Oatp1b2‐deficient mice further confirmed our results. Collectively, these findings demonstrate an important role for OATP1B1 in the systemic pharmacokinetics of multiple drugs used in the treatment of AML and suggest that inherited variability in host transporter function influences the effectiveness of therapy.
Severe dietary energy restriction is often used for overweight or obese individuals to achieve rapid weight loss and related health improvements. However, the extent of putative adverse effects on ...eating behaviour is unknown. We thus systematically searched seven databases for studies that assessed binge eating before and after severe dietary energy restriction (low or very low energy diets) in overweight or obese individuals. Fifteen clinically supervised interventions from 10 publications (nine of which involved only women) were included. Among individuals with clinically relevant pre‐treatment binge eating disorder, severe dietary energy restriction significantly decreased binge eating in all four interventions involving this population, at least during the weight loss programme. In contrast, no consistent association between severe dietary energy restriction and the onset of bingeing was found in 11 interventions involving individuals without pre‐treatment binge eating disorder, with four such interventions showing significant increases, two showing no change, and five showing significant decreases in binge eating. We conclude that clinically supervised severe dietary energy restriction appears safe and beneficial for overweight or obese individuals with pre‐treatment binge eating disorder, and does not necessarily trigger binge eating in those without binge eating disorder.
Magnetic influences increase in importance in the solar atmosphere from the photosphere out into the corona, yet our ability to routinely measure magnetic fields in the outer solar atmosphere is ...lacking. We describe the scientific objectives and capabilities of the COronal Solar Magnetism Observatory (COSMO), a proposed synoptic facility designed to measure magnetic fields and plasma properties in the large‐scale solar atmosphere. COSMO comprises a suite of three instruments chosen to enable the study of the solar atmosphere as a coupled system: (1) a coronagraph with a 1.5 m aperture to measure the magnetic field, temperature, density, and dynamics of the corona; (2) an instrument for diagnostics of chromospheric and prominence magnetic fields and plasma properties; and (3) a white light K‐coronagraph to measure the density structure and dynamics of the corona and coronal mass ejections. COSMO will provide a unique combination of magnetic field, density, temperature, and velocity observations in the corona and chromosphere that have the potential to transform our understanding of fundamental physical processes in the solar atmosphere and their role in the origins of solar variability and space weather.
Key Points
Society is becoming increasingly vulnerable to the effects of space weather
The physical processes responsible for solar activity remain poorly understood
COSMO will provide key measurements to advance our understanding of solar processes and activity
The international staging system (ISS) for multiple myeloma (MM) is a validated alternative to the Durie-Salmon staging system (DSS) for predicting survival at diagnosis. We compared these staging ...systems for predicting outcomes after upfront autologous stem cell transplantation by analyzing the outcomes of 729 patients between 1995 and 2002. With a median follow-up of 56 months, the univariate probabilities (95% CI) of non-relapse mortality (NRM), relapse, progression-free survival (PFS) and overall survival (OS) at 5 years were 7, 68, 25 and 52%, respectively. The median OS for stages I, II, III by DSS and ISS were 82, 68, 50 and 64, 68, 45 months, respectively. The concordance between the two staging systems was only 36%. Staging systems were formally compared using Cox models fit with DSS and ISS stages. The relative risks of PFS and OS were significantly different for stages I vs II and II vs III for DSS, but only for stages II vs III for ISS. Although both systems were predictive of PFS and OS, the DSS was superior in formal statistical comparison using Brier score. However, neither system was strongly predictive of outcomes, indicating the need for newer schemes incorporating other prognostic markers.
Mechanics of BCC and FCC hollow-sphere foams Sanders, W.S; Gibson, L.J
Materials science & engineering. A, Structural materials : properties, microstructure and processing,
07/2003, Letnik:
352, Številka:
1
Journal Article
Recenzirano
Hollow-sphere foams provide an alternative microstructure for low-density metal structures with the potential for improved properties. In a recent companion paper, the mechanical properties of ...hollow-sphere foams with simple cubic packing (SC) were shown to be close to the theoretical values for closed-cell foams and well above the measured modulus and strength of metallic closed-cell foams. Here, we analyze the elastic moduli and initial yield strength of body-centered cubic and face-centered cubic (FCC) packings of hollow-sphere foams. In general, the FCC packing gives the highest values of moduli and strengths.
An early invasive strategy is better than a conservative strategy, especially for higher-risk patients.
The syndrome of unstable angina and myocardial infarction without ST-segment elevation accounts ...for approximately 1.4 million hospital admissions annually in the United States and 2 million to 2.5 million worldwide.
1
Until fairly recently, initial treatment focused on medical stabilization through the use of antianginal and antithrombotic agents, including aspirin and unfractionated or low-molecular-weight heparin.
2
–
5
The next step is to decide whether to refer the patient for cardiac catheterization and revascularization, if appropriate (a routine invasive approach), or to follow a conservative strategy, in which cardiac procedures are performed only if the patient has spontaneous or provoked recurrent ischemia. There . . .
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