Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine as an analgesic are governed by CYP2D6 ...polymorphisms. Codeine has little therapeutic effect in patients who are CYP2D6 poor metabolizers, whereas the risk of morphine toxicity is higher in ultrarapid metabolizers. The purpose of this guideline (periodically updated at http://www.pharmgkb.org) is to provide information relating to the interpretation of CYP2D6 genotype test results to guide the dosing of codeine.
Background
Studies investigating the association between hospital volume and quality of gastric cancer surgery are lacking. In the present study, the effect of hospital volume on quality of gastric ...cancer surgery was evaluated by analysing data from the CRITICS (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) trial.
Methods
Patients who underwent gastrectomy with curative intent in the Netherlands were selected from the CRITICS trial database. Annual hospital volume of participating centres was derived from the Netherlands Cancer Registry. Hospital volume was categorized into very low (1–10 gastrectomies per year per institution), low (11–20), medium (21–30) and high (31 or more), and linked to the CRITICS database. Quality of surgery was analysed by surgicopathological compliance (removal of at least 15 lymph nodes), surgical compliance (removal of indicated lymph node stations) and the Maruyama Index. Postoperative morbidity and mortality were also compared between hospital categories.
Results
Between 2007 and 2015, 788 patients were included in the CRITICS study, of whom 494 were analysed. Surgicopathological compliance was higher (86·7 versus 50·4 per cent; P < 0·001), surgical compliance was greater (52·9 versus 19·8 per cent; P < 0·001) and median Maruyama Index was lower (0 versus 6; P = 0·006) in high‐volume hospitals compared with very low‐volume hospitals. There was no statistically significant difference in postoperative complications or mortality between the hospital volume categories.
Conclusion
Surgery performed in high‐volume hospitals was associated with better surgical quality than surgery carried out in lower‐volume hospitals.
High volume better quality
Global Monitoring for Environment and Security (GMES) is the European programme to establish a European capacity for Earth Observation. GMES is designed to provide European policy makers and public ...authorities with accurate and timely information to better manage the environment, understand and mitigate the effects of climate change and ensure civil security. Sentinel-3 is an Earth observation satellite mission specifically designed for GMES to ensure the long-term collection and operational delivery of high-quality measurements to GMES ocean, land, and atmospheric services, while contributing to the GMES, emergency and security services. Key Sentinel-3 measurement requirements, corresponding to identified GMES user needs, have been derived as follows:•Sea surface topography (SSH), significant wave height (Hs) and surface wind speed derived over the global ocean to an equivalent accuracy and precision as that presently achieved by ENVISAT Radar Altimeter-2 (RA-2) but with enhanced surface topography measurements in the coastal zone, sea ice regions and over inland rivers, their tributaries and lakes.•Sea surface temperature (SST) determined for oceanic and coastal waters globally to an equivalent accuracy and precision as that presently achieved by the ENVISAT Advanced Along Track Scanning Radiometer (AATSR) over the ocean (i.e. <0.3K), at a spatial resolution of 1km.•Visible, and Short-Wave Infrared radiances for oceanic, inland and coastal waters at a spatial resolution of 0.3km (simultaneously and co-registered with SST measurements), determined to an equivalent level of accuracy and precision as ENVISAT Medium Resolution Imaging Spectrometer with complete ocean coverage in 2–3days.•Visible and infrared radiances over global land-surfaces in 1–2days, sea-ice and ice-sheets equivalent to those currently provided from ENVISAT MERIS, AATSR and Système Probatoire d'Observation de la Terre (SPOT) Vegetation.
The Sentinel-3 mission addresses these requirements by implementing and operating:•A dual frequency, Synthetic Aperture Radar Altimeter (SRAL) instrument supported by a dual frequency passive microwave radiometer (MWR) for wet-tropospheric correction, a Precise Orbit Determination package including a GPS receiver, a DORIS instrument and a laser retro-reflector.•A highly sensitive Ocean and Land Colour Imager (OLCI) delivering multi-channel wide-swath optical measurements for ocean and land surfaces.•A dual-view Sea and Land Surface Temperature Radiometer (SLSTR) delivering accurate surface ocean, land, and ice temperature.•A collaborative ground segment providing management of the mission, management, development, production and access to core data products in an operational near real time delivery context.
The mission foresees a series of satellites, each having 7-year lifetime, over a 20-year period starting with the launch of Sentinel-3A in late 2013 and of Sentinel-3B in late 2014. During full operations two identical satellites will be maintained in the same orbit with a phase delay of 180°.
This paper provides an overview of the GMES Sentinel-3 mission including the mission background and user requirements, a technical description of the space segment, a brief overview of the ground segment concept, and a summary description of Sentinel-3 data products and their anticipated performance.
► A new satellite mission called Sentinel-3 dedicated to oceanography is described. ► A technical overview of the Sentinel-3 instrument payload is presented. ► A summary of the Sentinel-3 ground segment and operations concept is presented. ► A summary of products derived from Sentinel-3 payload instruments is presented.
Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are governed by CYP2D6 activity. Polymorphisms are ...a major cause of CYP2D6 variability. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for codeine based on CYP2D6 genotype. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2D6 genotype and codeine therapy.
Clinical Pharmacology & Therapeutics (2014); 95 4, 376–382. doi:10.1038/clpt.2013.254
Daratumumab is an anti-CD38 monoclonal antibody with lytic activity against multiple myeloma (MM) cells, including ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent ...cytotoxicity). Owing to a marked heterogeneity of response to daratumumab therapy in MM, we investigated determinants of the sensitivity of MM cells toward daratumumab-mediated ADCC and CDC. In bone marrow samples from 144 MM patients, we observed no difference in daratumumab-mediated lysis between newly diagnosed or relapsed/refractory patients. However, we discovered, next to an expected effect of effector (natural killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant association between CD38 expression and daratumumab-mediated ADCC (127 patients), as well as CDC (56 patients). Similarly, experiments with isogenic MM cell lines expressing different levels of CD38 revealed that the level of CD38 expression is an important determinant of daratumumab-mediated ADCC and CDC. Importantly, all-trans retinoic acid (ATRA) increased CD38 expression levels but also reduced expression of the complement-inhibitory proteins CD55 and CD59 in both cell lines and primary MM samples. This resulted in a significant enhancement of the activity of daratumumab in vitro and in a humanized MM mouse model as well. Our results provide the preclinical rationale for further evaluation of daratumumab combined with ATRA in MM patients.
The purpose of this guideline is to provide information for the interpretation of clinical dihydropyrimidine dehydrogenase (DPYD) genotype tests so that the results can be used to guide dosing of ...fluoropyrimidines (5‐fluorouracil and capecitabine). Detailed guidelines for the use of fluoropyrimidines, their clinical pharmacology, as well as analyses of cost‐effectiveness are beyond the scope of this document. The Clinical Pharmacogenetics Implementation Consortium (CPIC®) guidelines consider the situation of patients for which genotype data are already available (updates available at https://cpicpgx.org/guidelines/guideline‐for‐fluoropyrimidines‐and‐dpyd/).
ABSTRACT The Atacama Cosmology Telescope (ACT) makes high angular resolution measurements of anisotropies in the Cosmic Microwave Background (CMB) at millimeter wavelengths. We describe ACTPol, an ...upgraded receiver for ACT, which uses feedhorn-coupled, polarization-sensitive detector arrays, a 3° field of view, 100 mK cryogenics with continuous cooling, and meta material antireflection coatings. ACTPol comprises three arrays with separate cryogenic optics: two arrays at a central frequency of 148 GHz and one array operating simultaneously at both 97 GHz and 148 GHz. The combined instrument sensitivity, angular resolution, and sky coverage are optimized for measuring angular power spectra, clusters via the thermal Sunyaev-Zel'dovich (SZ) and kinetic SZ signals, and CMB lensing due to large-scale structure. The receiver was commissioned with its first 148 GHz array in 2013, observed with both 148 GHz arrays in 2014, and has recently completed its first full season of operations with the full suite of three arrays. This paper provides an overview of the design and initial performance of the receiver and related systems.
The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant ...indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin‐related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org).
The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, 'enhanced' ...cognitive-behavioral therapy (CBT-E).
Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat).
Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different.
ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.
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