To improve outcome of elderly patients with diffuse large B-cell lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14 trial.
Rituximab (375mg/m2) was given on days 0, 1, 4, ...8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results were to be compared with patients who had received the same chemotherapy in combination with eight 2-week applications of rituximab in RICOVER-60.
One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in considerably higher serum levels during the first 50 days of treatment, but rituximab exposure time was not prolonged. Grade 3 and 4 infections were exceptionally high in the first 20 patients without anti-infective prophylaxis, but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per patient; P = 0.007 and P = 0.125, respectively). Patients with international prognostic index = 3–5 had higher complete response/complete response unconfirmed rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population, but this did not translate into better long-term outcome, even though male hazard was decreased (event-free survival: from 1.5 to 1.1; progression-free survival: from 1.7 to 1.1; overall survival: from 1.4 to 1.0).
Dose-dense rituximab achieved higher rituximab serum levels, but was not more effective than eight 2-week applications in the historical control population, even though minor improvements in poor-prognosis and male patients cannot be excluded. The increased, though manageable toxicity, precludes its use in routine practice. Our results strongly support anti-infective prophylaxis with aciclovir and cotrimoxazole for all patients receiving R-CHOP.
The MASCOT Camera (MasCam) is part of the Mobile Asteroid Surface Scout (MASCOT) lander’s science payload. MASCOT has been launched to asteroid (162173) Ryugu onboard JAXA’s Hayabusa 2 asteroid ...sample return mission on Dec 3rd, 2014. It is scheduled to arrive at Ryugu in 2018, and return samples to Earth by 2020. MasCam was designed and built by DLR’s Institute of Planetary Research, together with Airbus-DS Germany. The scientific goals of the MasCam investigation are to provide ground truth for the orbiter’s remote sensing observations, provide context for measurements by the other lander instruments (radiometer, spectrometer and magnetometer), the orbiter sampling experiment, and characterize the geological context, compositional variations and physical properties of the surface (e.g. rock and regolith particle size distributions). During daytime, clear filter images will be acquired. During night, illumination of the dark surface is performed by an LED array, equipped with
4
×
36
monochromatic light-emitting diodes (LEDs) working in four spectral bands. Color imaging will allow the identification of spectrally distinct surface units. Continued imaging during the surface mission phase and the acquisition of image series at different sun angles over the course of an asteroid day will contribute to the physical characterization of the surface and also allow the investigation of time-dependent processes and to determine the photometric properties of the regolith. The MasCam observations, combined with the MASCOT hyperspectral microscope (MMEGA) and radiometer (MARA) thermal observations, will cover a wide range of observational scales and serve as a strong tie point between Hayabusa 2’s remote-sensing scales (
10
3
–
10
−
3
m
) and sample scales (
10
−
3
–
10
−
6
m
). The descent sequence and the close-up images will reveal the surface features over a broad range of scales, allowing an assessment of the surface’s diversity and close the gap between the orbital observations and those made by the in-situ measurements. The MasCam is mounted inside the lander slightly tilted, such that the center of its 54.8° square field-of-view is directed towards the surface at an angle of 22° with respect to the surface plane. This is to ensure that both the surface close to the lander and the horizon are observable. The camera optics is designed according to the Scheimpflug principle, thus that the entire scene along the camera’s depth of field (150 mm to infinity) is in focus. The camera utilizes a
1024
×
1024
pixel CMOS sensor sensitive in the 400–1000 nm wavelength range, peaking at 600–700 nm. Together with the f-16 optics, this yields a nominal ground resolution of 150 micron/px at 150 mm distance (diffraction limited). The camera flight model has undergone standard radiometric and geometric calibration both at the component and system (lander) level. MasCam relies on the use of wavelet compression to maximize data return within stringent mission downlink limits. All calibration and flight data products will be generated and archived in the Planetary Data System in PDS image format.
To investigate the relation between work environmental factors and the risk of major depressive disorder (MDD) over 1 year, the authors conducted a population-based longitudinal study of randomly ...selected employees in Alberta, Canada (January 2008 to November 2011). Participants without a current or lifetime diagnosis of MDD at baseline (n = 2,752) were followed for 1 year. MDD was assessed using the World Health Organization's Composite International Diagnostic Interview-Auto 2.1. The overall 1-year incidence of MDD was 3.6% (95% confidence interval: 2.8, 4.6); it was 2.9% (95% confidence interval: 1.9, 4.2) in men and 4.5% (95% confidence interval: 3.3, 6.2) in women. The relations between work environmental factors and MDD differed by sex. In men, high job strain increased the risk of MDD in those who worked 35-40 hours per week; job insecurity and family-to-work conflict were predictive of MDD. Women who worked 35-40 hours per week and reported job insecurity, a high effort-reward imbalance, and work-to-family conflict were at a higher risk of developing MDD. Job strain, effort-reward imbalance, job insecurity, and work-to-family conflicts are important risk factors for the onset of MDD and should be targets of primary prevention. However, these work environmental factors appear to operate differently in men and in women.
Patients with diffuse large B-cell lymphoma treated with first-line anthracycline-based immunochemotherapy and remaining in remission at 2 years have excellent outcomes. This study assessed overall ...survival (OS) stratified by progression-free survival (PFS) at 24months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the Surrogate Endpoint for Aggressive Lymphoma (SEAL) Collaboration.
PFS24 was defined as being alive and PFS24 after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared with each patient’s age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs).
A total of 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62years (range 18–92), and 56% were greater than 60years of age. At a median follow-up of 4.4years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. A total of 1423 assessable patients failed to achieve PFS24 with a median OS of 7.2months (95% CI 6.8–8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI 30.0–34.4). A total of 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI 1.09–1.37). The observed OS versus expected OS at 3, 5, and 7years after achieving PFS24 was 93.1% versus 94.4%, 87.6% versus 89.5%, and 80.0% versus 83.7%, respectively.
Patients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for 7 years after achieving PFS24.
After its release and a descent and bouncing phase, the Hayabusa2 lander MASCOT came to a final rest and MASCOT’s camera MASCam acquired a set of images of the surface of Ryugu. With MASCam’s ...instantaneous field of view of about 1 mrad, the images provide pixel scales from 0.2 to 0.5 mm pixel−1 in the foreground and up to 1 cm pixel−1 for surface parts in the background. Using a stereo-photogrammetric analysis of the MASCam images taken from slightly different positions due to commanded and unintentional movements of the MASCOT lander, we were able to determine the orientation for the different measurement positions. Furthermore, we derived a 3D surface model of MASCOT’s vicinity. Although the conditions for 3D stereo processing were poor due to very small stereo angles, the derived 3D model has about 0.5 cm accuracy in the foreground at 20 cm distance and about 1.5 cm at a distance of 40–50 cm.
Objective
To test whether duration of untreated psychosis (DUP) < 3 months, recommended by the World Health Organization/International Early Psychosis Association, enhances the effects of an extended ...early intervention service (EEIS) on symptom remission.
Method
We examined data from a randomized controlled trial in which patients who received 2 years of treatment in EIS for psychosis were subsequently randomized to either 3 years of EEIS or 3 years of regular care (RC). Using a DUP cut‐off ≤ 12 weeks (approximately < 3 months), patients were split into two groups. Length of positive, negative and total symptom remission were the outcomes.
Results
Patients (N = 217) were mostly male (68%) with schizophrenia spectrum disorder (65%); 108 (50%) received EEIS (58 had DUP ≤12 weeks; 50 had DUP >12 weeks). Interaction between treatment condition (EEIS vs. RC) and DUP cut‐off ≤ 12 weeks was only significant in multiple linear regression model examining length of negative symptom remission as the outcome (adjusted β = 36.88 SE = 15.88, t = 2.32, P = 0.02). EEIS patients with DUP ≤12 weeks achieved 25 more weeks of negative symptom remission than EEIS patients with DUP >12 weeks.
Conclusion
Having a short DUP may be critical in deriving long‐term benefits from EIS for psychosis, including EEIS settings. This work empirically supports policy recommendations of reducing DUP <3 months.
The selective serotonin reuptake inhibitor escitalopram (ESC) is indicated for the treatment of major depressive disorder (MDD) and of generalized anxiety disorder (GAD). Monitoring of blood levels ...(BLs) is strongly indicated due to ESC’s high interindividual pharmacokinetic variability. The aim of this study was to analyse clinical efficacy and pharmacokinetic influences on ESC BLs, in patients with depressive disorder alone and with comorbid alcohol or benzodiazepine use disorder. Data were collected from patients treated under naturalistic conditions for whom Therapeutic Drug Monitoring (TDM) was requested to guide antidepressant drug therapy and analysed retrospectively. Particular emphasis was given to patients with alcohol or benzodiazepine use disorder. Responders according to the clinical global impression (CGI) scale were compared with nonresponders for their ESC blood level (BL). The patient sample included 344 patients from 16 psychiatric hospitals in Germany. Influencing factors that could explain 22% of ESC BLs were dose, sex and age. Variability was high between individuals, and doses up to 40 mg were common in real-world settings. Patients treated with ESC monotherapy who responded showed a trend towards higher BLs compared to nonresponders with a concentration of 15 ng/mL separating both groups. Pathological changes in liver function (indicated by elevated GGT in combination with an AST/ALT ratio ≥ 1) resulted in higher dose-corrected ESC concentrations. Influencing factors that could explain 22% of ESC blood levels were dose, sex, and age. Our findings confirm the currently recommended lower threshold level and support the need for standard TDM analyses in everyday clinical practice. The ICD 10 diagnosis alcohol dependence alone does not lead to pharmacokinetic changes in the metabolism of ESC, but altered liver function does.
Positron emission tomography (PET) has been used since the late 1980s for the assessment of relationships between occupancy of D
receptors by antipsychotic drugs in the human brain and the clinical ...effects and side effects of these compounds in patients. It is now well established for most D
antagonists, both of the first and the second generation, that the ideal occupancy of their target receptors is between approximately 65 and 80%. If the occupancy is below 65%, the probability of treatment response is reduced, if the occupancy is higher than 80%, the risk for extrapyramidal side-effects increases substantially. However, partial agonist antipsychotics behave different from these rules. It has been shown for all three available drugs of this class (aripiprazole, brexpiprazole, cariprazine) that, due to their special pharmacology, a very high target engagement (>90%) not only is not harmful but represents a prerequisite for antipsychotic efficacy. The available PET studies for these drugs are reviewed in this work. It is demonstrated that optimal plasma levels for partial agonist antipsychotics can be derived from these studies, which can guide individual treatment in routine patient care.
Major depression is a prevalent mental disorder in the working population. Improving the work environment may reduce the risk of major depression. The authors examined data from the longitudinal ...cohort of the Canadian National Population Health Survey from 1994–1995 to 2004–2005. Survey participants were classified into 4 groups by changes in job strain status from 1994–1995 to 2000–2001 (no change in low job strain, no change in high job strain, changing from high to low job strain, and changing from low to high job strain). The incidence proportion of major depressive episodes in each of the 4 groups was 4.0%, 8.0%, 4.4%, and 6.9%, respectively. Participants who reported a change from high to low job strain had a risk of major depression similar to those exposed to persistently low job strain. Among those exposed to persistent high job strain, only participants who reported good or excellent health at baseline had a higher risk of major depression, but those who reported fair or poor health did not. Reducing job strain may have positive impacts on the risk of depression. Self-rated health is a strong predictor of depression and plays an important role in the relation between job strain and depression.
PDF
