Treat-to-target in systemic lupus erythematosus: recommendations from an international task force.

The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE

A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS)

Objectives Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. Methods An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. Results The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions: 1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by . (reference to symptoms, signs, routine labs). 2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment. 3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics. The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. Conclusions The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes

2021 DORIS definition of remission in SLE: final recommendations from an international task force.

OBJECTIVE: To achieve consensus on a definition of remission in SLE (DORIS). BACKGROUND: Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. METHODS: Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. RESULTS: Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. CONCLUSION: The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Analyse des données post-sismiques terre-mer du séisme de Pedernales 2016 Mw=7.8 (Équateur) : une clef pour comprendre les supercycles sismiques

The Ecuador-Colombian subduction zone has hosted a series of large subduction earthquakes over the course of the 20th century. This earthquake sequence started in 1906 with a Mw 8.4-8.8 earthquake, which ruptured a 200-500 km long segment of the megathrust. It was followed by three large earthquakes that broke, from south to north, portions already contained in the 1906 rupture. These earthquakes occurred in 1942 (Mw=7.8), 1958 (Mw=7.6) and 1979 (Mw=8.2), respectively. In 2016, the Pedernales earthquake re-ruptured the 1942 coseismic region, possibly starting a new cascade of large events.The Pedernales earthquake and its aftershocks, recorded thanks to the international deployment of seismic stations in the months following the mainshock, provide an opportunity to better understand the seismotectonic processes that occur in the region. This thesis will focus primarily on the interactions between seismicity and aseismic slip, and on the influence of the structure of the megathrust on the seismic activity.For this purpose, a catalogue of repeating earthquakes was created by correlating the existing aftershock catalogue. The families of repeating earthquakes were then completed using template-matching to find missing events. Repeating earthquakes were then relocated in a 1D model, first using manual picks and then using differential times from correlations. Finally, source properties were determined for a portion of the aftershock catalogue.Repeating earthquakes in Ecuador occur primarily within larger aftershock clusters situated at the edge of the main afterslip regions. Additionally, the slip associated with individual repeating earthquake families seems to have an indirect link to the slip modelled using GPS data. Indeed, family slip appears heterogeneous, suggesting perhaps a more complex link between afterslip and repeating earthquakes, and likely reflecting the complexity of the megathrust structure.Additionally, the study of source properties of Pedernales aftershocks reveals a segmentation of the subduction zone with distance to the trench. Stress drops near the trench are low, and decrease with time during the postseismic period, as observed within families of repeating earthquakes. This is probably due to a variation in pore fluid pressure, which is likely very high near the trench, and which plays a crucial role in seismogenesis in the region.La zone de subduction qui s'étend du nord de l'Equateur au sud de la Colombie a subi une séquence de grands séismes au cours du XXe siècle. Cette séquence débute en 1906 avec un séisme de magnitude 8.4-8.8, qui rompt une portion du chevauchement d'interplaque d'environ 200-500 km de long. S'ensuit ensuite trois grand séismes de magnitudes 7.6 à 8.2, qui rompent à nouveau cette zone du sud au nord en 1942, 1958 et 1979. Cette séquence est à nouveau amorcée en 2016 lorsque le séisme de Pedernales casse la zone de rupture du séisme de 1942, marquant ainsi peut-être le début d'une nouvelle cascade sismique.Le séisme de Pedernales et ses répliques, enregistrées grâce au déploiement de stations sismiques dans les mois suivant le séisme, permettent de mieux comprendre la zone. Cette thèse s'intéresse tout particulièrement aux interactions entre sismicité et glissement asismique dans la région, ainsi qu'au lien entre la sismicité et la structure de la zone de subduction.Pour ce faire, un catalogue de séismes répétitifs est élaboré par corrélation à partir du catalogue de répliques existant. Les données sont également scannées par template-matching afin de compléter les familles de séismes répétitifs. Ceux-ci sont ensuite relocalisés dans un modèle de vitesse 1D grâce à des pointés manuels et à des temps relatifs d'arrivée. Enfin, nous déterminons les propriétés de sources d'une partie des répliques de Pedernales.Les séismes répétitifs en Equateur ont lieu principalement au sein de clusters de sismicité, en marge des zones de glissement post-sismique. Par ailleurs, le glissement associé aux familles individuelles de séismes répétés ne semble pas avoir de lien direct avec le glissement modélisé à l'aide de données GNSS. Il semble au contraire être bien plus hétérogène, laissant penser à un lien plus complexe entre glissement asismique et séismes répétitifs, et reflétant probablement une géométrie complexe de la zone de subduction.Par ailleurs, l'étude des propriétés de sources des répliques de Pedernales met en évidence une segmentation de la zone de subduction basée sur la distance à la fosse. Les chutes de contrainte des séismes près de la fosse sont basses, et diminuent au cours du temps durant la période postsismique, comme le montre l'étude des séismes répétitifs. Cela est probablement dû à une variation de pression des fluides, qui sont très abondants au niveau de la fosse, et qui jouent un rôle crucial dans le comportement sismogène de la zone

Onshore-offshore post-seismic data analysis of the Mw=7.8 2016 Pedernales earthquake (Ecuador) : key to understanding earthquake supercycles

La zone de subduction qui s'étend du nord de l'Equateur au sud de la Colombie a subi une séquence de grands séismes au cours du XXe siècle. Cette séquence débute en 1906 avec un séisme de magnitude 8.4-8.8, qui rompt une portion du chevauchement d'interplaque d'environ 200-500 km de long. S'ensuit ensuite trois grand séismes de magnitudes 7.6 à 8.2, qui rompent à nouveau cette zone du sud au nord en 1942, 1958 et 1979. Cette séquence est à nouveau amorcée en 2016 lorsque le séisme de Pedernales casse la zone de rupture du séisme de 1942, marquant ainsi peut-être le début d'une nouvelle cascade sismique.Le séisme de Pedernales et ses répliques, enregistrées grâce au déploiement de stations sismiques dans les mois suivant le séisme, permettent de mieux comprendre la zone. Cette thèse s'intéresse tout particulièrement aux interactions entre sismicité et glissement asismique dans la région, ainsi qu'au lien entre la sismicité et la structure de la zone de subduction.Pour ce faire, un catalogue de séismes répétitifs est élaboré par corrélation à partir du catalogue de répliques existant. Les données sont également scannées par template-matching afin de compléter les familles de séismes répétitifs. Ceux-ci sont ensuite relocalisés dans un modèle de vitesse 1D grâce à des pointés manuels et à des temps relatifs d'arrivée. Enfin, nous déterminons les propriétés de sources d'une partie des répliques de Pedernales.Les séismes répétitifs en Equateur ont lieu principalement au sein de clusters de sismicité, en marge des zones de glissement post-sismique. Par ailleurs, le glissement associé aux familles individuelles de séismes répétés ne semble pas avoir de lien direct avec le glissement modélisé à l'aide de données GNSS. Il semble au contraire être bien plus hétérogène, laissant penser à un lien plus complexe entre glissement asismique et séismes répétitifs, et reflétant probablement une géométrie complexe de la zone de subduction.Par ailleurs, l'étude des propriétés de sources des répliques de Pedernales met en évidence une segmentation de la zone de subduction basée sur la distance à la fosse. Les chutes de contrainte des séismes près de la fosse sont basses, et diminuent au cours du temps durant la période postsismique, comme le montre l'étude des séismes répétitifs. Cela est probablement dû à une variation de pression des fluides, qui sont très abondants au niveau de la fosse, et qui jouent un rôle crucial dans le comportement sismogène de la zone.The Ecuador-Colombian subduction zone has hosted a series of large subduction earthquakes over the course of the 20th century. This earthquake sequence started in 1906 with a Mw 8.4-8.8 earthquake, which ruptured a 200-500 km long segment of the megathrust. It was followed by three large earthquakes that broke, from south to north, portions already contained in the 1906 rupture. These earthquakes occurred in 1942 (Mw=7.8), 1958 (Mw=7.6) and 1979 (Mw=8.2), respectively. In 2016, the Pedernales earthquake re-ruptured the 1942 coseismic region, possibly starting a new cascade of large events.The Pedernales earthquake and its aftershocks, recorded thanks to the international deployment of seismic stations in the months following the mainshock, provide an opportunity to better understand the seismotectonic processes that occur in the region. This thesis will focus primarily on the interactions between seismicity and aseismic slip, and on the influence of the structure of the megathrust on the seismic activity.For this purpose, a catalogue of repeating earthquakes was created by correlating the existing aftershock catalogue. The families of repeating earthquakes were then completed using template-matching to find missing events. Repeating earthquakes were then relocated in a 1D model, first using manual picks and then using differential times from correlations. Finally, source properties were determined for a portion of the aftershock catalogue.Repeating earthquakes in Ecuador occur primarily within larger aftershock clusters situated at the edge of the main afterslip regions. Additionally, the slip associated with individual repeating earthquake families seems to have an indirect link to the slip modelled using GPS data. Indeed, family slip appears heterogeneous, suggesting perhaps a more complex link between afterslip and repeating earthquakes, and likely reflecting the complexity of the megathrust structure.Additionally, the study of source properties of Pedernales aftershocks reveals a segmentation of the subduction zone with distance to the trench. Stress drops near the trench are low, and decrease with time during the postseismic period, as observed within families of repeating earthquakes. This is probably due to a variation in pore fluid pressure, which is likely very high near the trench, and which plays a crucial role in seismogenesis in the region

Analyse des données post-sismiques terre-mer du séisme de Pedernales 2016 Mw=7.8 (Équateur) : une clef pour comprendre les supercycles sismiques

The Ecuador-Colombian subduction zone has hosted a series of large subduction earthquakes over the course of the 20th century. This earthquake sequence started in 1906 with a Mw 8.4-8.8 earthquake, which ruptured a 200-500 km long segment of the megathrust. It was followed by three large earthquakes that broke, from south to north, portions already contained in the 1906 rupture. These earthquakes occurred in 1942 (Mw=7.8), 1958 (Mw=7.6) and 1979 (Mw=8.2), respectively. In 2016, the Pedernales earthquake re-ruptured the 1942 coseismic region, possibly starting a new cascade of large events.The Pedernales earthquake and its aftershocks, recorded thanks to the international deployment of seismic stations in the months following the mainshock, provide an opportunity to better understand the seismotectonic processes that occur in the region. This thesis will focus primarily on the interactions between seismicity and aseismic slip, and on the influence of the structure of the megathrust on the seismic activity.For this purpose, a catalogue of repeating earthquakes was created by correlating the existing aftershock catalogue. The families of repeating earthquakes were then completed using template-matching to find missing events. Repeating earthquakes were then relocated in a 1D model, first using manual picks and then using differential times from correlations. Finally, source properties were determined for a portion of the aftershock catalogue.Repeating earthquakes in Ecuador occur primarily within larger aftershock clusters situated at the edge of the main afterslip regions. Additionally, the slip associated with individual repeating earthquake families seems to have an indirect link to the slip modelled using GPS data. Indeed, family slip appears heterogeneous, suggesting perhaps a more complex link between afterslip and repeating earthquakes, and likely reflecting the complexity of the megathrust structure.Additionally, the study of source properties of Pedernales aftershocks reveals a segmentation of the subduction zone with distance to the trench. Stress drops near the trench are low, and decrease with time during the postseismic period, as observed within families of repeating earthquakes. This is probably due to a variation in pore fluid pressure, which is likely very high near the trench, and which plays a crucial role in seismogenesis in the region.La zone de subduction qui s'étend du nord de l'Equateur au sud de la Colombie a subi une séquence de grands séismes au cours du XXe siècle. Cette séquence débute en 1906 avec un séisme de magnitude 8.4-8.8, qui rompt une portion du chevauchement d'interplaque d'environ 200-500 km de long. S'ensuit ensuite trois grand séismes de magnitudes 7.6 à 8.2, qui rompent à nouveau cette zone du sud au nord en 1942, 1958 et 1979. Cette séquence est à nouveau amorcée en 2016 lorsque le séisme de Pedernales casse la zone de rupture du séisme de 1942, marquant ainsi peut-être le début d'une nouvelle cascade sismique.Le séisme de Pedernales et ses répliques, enregistrées grâce au déploiement de stations sismiques dans les mois suivant le séisme, permettent de mieux comprendre la zone. Cette thèse s'intéresse tout particulièrement aux interactions entre sismicité et glissement asismique dans la région, ainsi qu'au lien entre la sismicité et la structure de la zone de subduction.Pour ce faire, un catalogue de séismes répétitifs est élaboré par corrélation à partir du catalogue de répliques existant. Les données sont également scannées par template-matching afin de compléter les familles de séismes répétitifs. Ceux-ci sont ensuite relocalisés dans un modèle de vitesse 1D grâce à des pointés manuels et à des temps relatifs d'arrivée. Enfin, nous déterminons les propriétés de sources d'une partie des répliques de Pedernales.Les séismes répétitifs en Equateur ont lieu principalement au sein de clusters de sismicité, en marge des zones de glissement post-sismique. Par ailleurs, le glissement associé aux familles individuelles de séismes répétés ne semble pas avoir de lien direct avec le glissement modélisé à l'aide de données GNSS. Il semble au contraire être bien plus hétérogène, laissant penser à un lien plus complexe entre glissement asismique et séismes répétitifs, et reflétant probablement une géométrie complexe de la zone de subduction.Par ailleurs, l'étude des propriétés de sources des répliques de Pedernales met en évidence une segmentation de la zone de subduction basée sur la distance à la fosse. Les chutes de contrainte des séismes près de la fosse sont basses, et diminuent au cours du temps durant la période postsismique, comme le montre l'étude des séismes répétitifs. Cela est probablement dû à une variation de pression des fluides, qui sont très abondants au niveau de la fosse, et qui jouent un rôle crucial dans le comportement sismogène de la zone

Analyse des données post-sismiques terre-mer du séisme de Pedernales 2016 Mw=7.8 (Équateur) : une clef pour comprendre les supercycles sismiques

The Ecuador-Colombian subduction zone has hosted a series of large subduction earthquakes over the course of the 20th century. This earthquake sequence started in 1906 with a Mw 8.4-8.8 earthquake, which ruptured a 200-500 km long segment of the megathrust. It was followed by three large earthquakes that broke, from south to north, portions already contained in the 1906 rupture. These earthquakes occurred in 1942 (Mw=7.8), 1958 (Mw=7.6) and 1979 (Mw=8.2), respectively. In 2016, the Pedernales earthquake re-ruptured the 1942 coseismic region, possibly starting a new cascade of large events.The Pedernales earthquake and its aftershocks, recorded thanks to the international deployment of seismic stations in the months following the mainshock, provide an opportunity to better understand the seismotectonic processes that occur in the region. This thesis will focus primarily on the interactions between seismicity and aseismic slip, and on the influence of the structure of the megathrust on the seismic activity.For this purpose, a catalogue of repeating earthquakes was created by correlating the existing aftershock catalogue. The families of repeating earthquakes were then completed using template-matching to find missing events. Repeating earthquakes were then relocated in a 1D model, first using manual picks and then using differential times from correlations. Finally, source properties were determined for a portion of the aftershock catalogue.Repeating earthquakes in Ecuador occur primarily within larger aftershock clusters situated at the edge of the main afterslip regions. Additionally, the slip associated with individual repeating earthquake families seems to have an indirect link to the slip modelled using GPS data. Indeed, family slip appears heterogeneous, suggesting perhaps a more complex link between afterslip and repeating earthquakes, and likely reflecting the complexity of the megathrust structure.Additionally, the study of source properties of Pedernales aftershocks reveals a segmentation of the subduction zone with distance to the trench. Stress drops near the trench are low, and decrease with time during the postseismic period, as observed within families of repeating earthquakes. This is probably due to a variation in pore fluid pressure, which is likely very high near the trench, and which plays a crucial role in seismogenesis in the region.La zone de subduction qui s'étend du nord de l'Equateur au sud de la Colombie a subi une séquence de grands séismes au cours du XXe siècle. Cette séquence débute en 1906 avec un séisme de magnitude 8.4-8.8, qui rompt une portion du chevauchement d'interplaque d'environ 200-500 km de long. S'ensuit ensuite trois grand séismes de magnitudes 7.6 à 8.2, qui rompent à nouveau cette zone du sud au nord en 1942, 1958 et 1979. Cette séquence est à nouveau amorcée en 2016 lorsque le séisme de Pedernales casse la zone de rupture du séisme de 1942, marquant ainsi peut-être le début d'une nouvelle cascade sismique.Le séisme de Pedernales et ses répliques, enregistrées grâce au déploiement de stations sismiques dans les mois suivant le séisme, permettent de mieux comprendre la zone. Cette thèse s'intéresse tout particulièrement aux interactions entre sismicité et glissement asismique dans la région, ainsi qu'au lien entre la sismicité et la structure de la zone de subduction.Pour ce faire, un catalogue de séismes répétitifs est élaboré par corrélation à partir du catalogue de répliques existant. Les données sont également scannées par template-matching afin de compléter les familles de séismes répétitifs. Ceux-ci sont ensuite relocalisés dans un modèle de vitesse 1D grâce à des pointés manuels et à des temps relatifs d'arrivée. Enfin, nous déterminons les propriétés de sources d'une partie des répliques de Pedernales.Les séismes répétitifs en Equateur ont lieu principalement au sein de clusters de sismicité, en marge des zones de glissement post-sismique. Par ailleurs, le glissement associé aux familles individuelles de séismes répétés ne semble pas avoir de lien direct avec le glissement modélisé à l'aide de données GNSS. Il semble au contraire être bien plus hétérogène, laissant penser à un lien plus complexe entre glissement asismique et séismes répétitifs, et reflétant probablement une géométrie complexe de la zone de subduction.Par ailleurs, l'étude des propriétés de sources des répliques de Pedernales met en évidence une segmentation de la zone de subduction basée sur la distance à la fosse. Les chutes de contrainte des séismes près de la fosse sont basses, et diminuent au cours du temps durant la période postsismique, comme le montre l'étude des séismes répétitifs. Cela est probablement dû à une variation de pression des fluides, qui sont très abondants au niveau de la fosse, et qui jouent un rôle crucial dans le comportement sismogène de la zone

Spatio‐Temporal Evolution of Aftershock and Repeater Source Properties After the 2016 Pedernales Earthquake (Ecuador)

International audienceSectionsPDFPDFToolsShareAbstractSubduction zones are highly heterogeneous regions capable of hosting large earthquakes. To better constrain the processes at depth, we analyze the source properties of 1514 aftershocks of the 16th April 2016 Mw 7.8 Pedernales earthquake (Ecuador) using spectral ratios. We are able to retrieve accurate seismic moments, stress drops, and P and S corner frequencies for 341 aftershocks, including 136 events belonging to families of repeating earthquakes. We find that, for the studied magnitude range (Mw 2–4), stress drops appear to increase as a function of seismic moment. They are also found to depend on their distance to the trench. This is in part explained by the increase in depth, and therefore normal stress, away from the trench. However, even accounting for the shallow depths of earthquakes, stress drops appear to be anomalously low near the trench, which can be explained by a high pore fluid pressure or by inherent properties of the medium (low coefficient of friction/low rigidity of the medium) in that region. We are also able to examine the temporal evolution of source properties thanks to the presence of repeating earthquakes. We find that the variations of source properties within repeating earthquake families are not uniform, and are highly spatially variable over most of the study area. This is not the case near the trench, however, where stress drops systematically decrease over time. We suggest that this reflects an increase in pore fluid pressure near the trench over the postseismic period