Anorexia Nervosa in Adolescence: A Comprehensive Study of Multidimensional Factors Associated with Symptom Severity 1 Year Following the Diagnosis.

The overarching goal of this study was to examine the unique contribution of psychological, familial, and friendship factors in explaining anorexia nervosa (AN) symptom severity 1 year following diagnosis among a sample of adolescent girls. A second objective was to determine whether friendship factors mediated the association between psychological and/or familial factors and AN symptom severity. This study included 143 adolescent girls under the age of 18 diagnosed with AN (M = 14.84, SD = 1.31). Participants were recruited from specialized eating disorder treatment programs. At admission (T1), participants completed a set of self-report questionnaires measuring psychological, familial, and friendship factors. AN symptom severity was assessed 1 year later (T2). Results of hierarchical regression analysis revealed that greater general psychological maladjustment at T1 (b = .26; se = .03; p = .00) was associated with greater AN symptom severity at T2. Greater alienation from friends at T1 (b = 1.20, se = .53, p = .03) also predicted greater AN symptom severity at T2, above and beyond the influence of adolescent girls' general psychological maladjustment. Finally, the mediating role of alienation from friends in the association between general psychological maladjustment at T1 and AN symptom severity at T2 was also identified. AN is a multidimensional disorder with a prognosis that involves both psychological and social factors. The results stemming from the present study shed light on the role of peer as a mechanism through which general psychological maladjustment is linked to AN symptom severity 1 year following diagnosis.

Assessment of DOAC in GEriatrics (Adage Study): Rivaroxaban/Apixaban Concentrations and Thrombin Generation Profiles in NVAF Very Elderly Patients.

BACKGROUND: Although a growing number of very elderly patients with atrial fibrillation (AF), multiple conditions, and polypharmacy receive direct oral anticoagulants (DOACs), few studies specifically investigated both apixaban/rivaroxaban pharmacokinetics and pharmacodynamics in such patients. AIMS: To investigate: (1) DOAC concentration-time profiles; (2) thrombin generation (TG); and (3) clinical outcomes 6 months after inclusion in very elderly AF in-patients receiving rivaroxaban or apixaban. METHODS: Adage-NCT02464488 was an academic prospective exploratory multicenter study, enrolling AF in-patients aged ≥80 years, receiving DOAC for at least 4 days. Each patient had one to five blood samples at different time points over 20 days. DOAC concentrations were determined using chromogenic assays. TG was investigated using ST-Genesia (STG-ThromboScreen, STG-DrugScreen). RESULTS: We included 215 patients (women 71.1%, mean age: 87 ± 4 years), 104 rivaroxaban and 111 apixaban, and 79.5% receiving reduced-dose regimen. We observed important inter-individual variabilities (coefficient of variation) whatever the regimen, at C max [49-46%] and C min [75-61%] in 15 mg rivaroxaban and 2.5 mg apixaban patients, respectively. The dose regimen was associated with C max and C min plasma concentrations in apixaban (p = 0.0058 and p = 0.0222, respectively), but not in rivaroxaban samples (multivariate analysis). Moreover, substantial variability of thrombin peak height (STG-ThromboScreen) was noticed at a given plasma concentration for both xabans, suggesting an impact of the underlying coagulation status on TG in elderly in-patients. After 6-month follow-up, major bleeding/thromboembolic event/death rates were 6.7%/1.0%/17.3% in rivaroxaban and 5.4%/3.6%/18.9% in apixaban patients, respectively. CONCLUSION: Our study provides original data in very elderly patients receiving DOAC in a real-life setting, showing great inter-individual variability in plasma concentrations and TG parameters. Further research is needed to understand the potential clinical impact of these findings.

[An innovative process for sustaining and scaling up a school-based mental health promotion and anxiety prevention programs: The example of the HORS-PISTE program]. / Processus novateur pour favoriser la pérennisation et la mise à l'échelle de programmes de prévention de l'anxiété à l'école : l'exemple du programme HORS-PISTE.

Context Anxiety disorders are among the most prevalent psychopathologies for children and adolescents in Quebec. The prevalence of anxiety disorders is very high and has been affecting a growing number of young people for the past 10 years. It is possible to observe an increased number of anxiety prevention programs for young people around the world. However, some authors point out that they are rarely faithfully implemented, sustained, and scaled up in several schools. Based on implementation science, this HORS-PISTE program was developed to address these important issues by preventing anxiety in Quebec high school students. Implemented in more than 100 schools, the program is now part of Action 4.3 (Promote the deployment of the HORS-PISTE program) of the new interdepartmental Action Plan on Mental Health of the Government of Quebec (2022). Purpose This article aims to describe how the Knowledge-to-Action (KTA) framework, derived of implementation science, was used to design, implement, sustain, evaluate, and scale up the HORS-PISTE program. This framework proposes a cyclical process in seven phases. Method A multi-method and multi-stakeholder approach was conducted with a grant from the Public Health Agency of Canada's Mental Health Promotion Innovation Fund, which has been supporting 20 innovative projects across Canada since 2019. It includes a pre-post evaluation protocol consisting of validated questionnaires, surveys (administered to students, parents, and teachers), semi-structured logbooks completed by program facilitators and implementation review meetings in each school. The different cycles of the program development, implementation and evaluation are discussed through the KTA framework phases. Results From 2017 to 2021, this methodology made it possible to evaluate and readjust the program each year to promote its adaptation and prepare its scaling up. This article highlights the data collected and analyzed in relation to the seven phases of the KTA framework. Conclusion This article demonstrates how implementation science can support designers of anxiety prevention programs who are concerned by scaling up and sustaining their programs. Issues in combining the scientific rigor of evaluation with the reality of the field are also raised.

Ticagrelor reversal: in vitro assessment of four haemostatic agents.

AIM: Management of ticagrelor-induced bleeding is challenging as platelet transfusion is ineffective. An effective strategy is needed. This study aimed to investigate in vitro the efficacy of four haemostatic drugs (HDs), namely recombinant activated factor VII (rFVIIa), fibrinogen concentrate (Fib), tranexamic acid (TXA) and factor XIII concentrate (FXIII) to improve the haemostatic capacity in the presence of ticagrelor. METHODS: Blood was spiked with ticagrelor then supplemented by either HD or control. Several assays were performed: ADP-induced platelet aggregation measured by impedance aggregometry, light transmission and two global assays, thrombolastography with the platelet mapping device (TEG-PM) and a platelet-dependent thrombin generation assay (TGA). RESULTS: Ticagrelor inhibited ADP-induced platelet aggregation and decreased the clot strength maximum amplitude (MA) in TEG-PMADP. None of the HDs corrected these parameters. However, rFVIIa shortened the coagulation time R using TEG-PMthrombin and the time to peak prolonged by ticagrelor in TGA. Fib increased MAthrombin and FXIII decreased LY30. TXA had no effects. CONCLUSIONS: Whereas none of the HDs corrected ticagrelor-induced platelet inhibition, rFVIIa shortened coagulation times, Fib increased clot firmness and FXIII decreased fibrinolysis. Consequently, they may bypass ticagrelor effects by acting on fibrin formation or fibrinolysis. Further studies are needed to confirm these data in vivo.

Assessment of haemostasis in patients with cirrhosis: Relevance of the ROTEM tests?: A prospective, cross-sectional study.

BACKGROUND: In patients with cirrhosis, decreased rotational thromboelastometry (ROTEM) parameters suggest hypocoagulability secondary to liver dysfunction. However, observed normal or increased thrombin generation suggests preserved haemostasis and/or a procoagulant state. The correlated levels of both coagulation factors and inhibitors also support preserved haemostasis. OBJECTIVE: The objective of this study is to investigate the correlation between three specific approaches of haemostasis (ROTEM, thrombin generation and coagulation factors/inhibitors) on the same plasma sample from patients with cirrhosis. DESIGN: A prospective, observational study. SETTING: Single university hospital. PARTICIPANTS: Forty patients with cirrhosis. INTERVENTION: Measurement of the following factors: model for end-stage liver disease (MELD) scores; ROTEM maximum clot firmness (ROTEM-MCF) in EXTEM, INTEM, FIBTEM assays; fibrinogen; factors V and VIII; von Willebrand factor; protein C; protein S; antithrombin; and the thrombin generation test (TGT) enabling the calculation of endogenous thrombin potential without and with thrombomodulin, and the ratio of endogenous thrombin potential with-to-without thrombomodulin (regarded as an index of hypercoagulability). RESULTS: ROTEM-MCF values were distributed within the normal and hypocoagulation ranges; were correlated to variations in factor V, fibrinogen, protein C and S and antithrombin; and were inversely correlated to MELD scores (ρ > 0.5; P < 0.05). Levels of von Willebrand factor were above normal and were not correlated with any other factor levels. After addition of thrombomodulin, endogenous thrombin potential values were distributed within or above normal values. Factor V variation was correlated to the ratio of endogenous thrombin potential with-to-without thrombomodulin. CONCLUSION: ROTEM indicated hypocoagulability correlated to liver dysfunction. In contrast, the TGT indicated a preserved or even increased coagulation profile (which was supported by the correlation between coagulant factors and inhibitors) and a potential for hypercoagulability inversely correlated to the degree of liver dysfunction. ROTEM may not be appropriate for haemostasis assessment in patients with liver cirrhosis and could lead to the unnecessary transfusion of fresh frozen plasma. TRIAL REGISTRATION: S.C. 3024 - ID RCB: 2012-A01728-35.

Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group.

The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.

Magnetic resonance imaging assessment of spinal cord and cauda equina motion in supine patients with spinal metastases planned for spine stereotactic body radiation therapy.

PURPOSE: To assess motion of the spinal cord and cauda equina, which are critical neural tissues (CNT), which is important when evaluating the planning organ-at-risk margin required for stereotactic body radiation therapy. METHODS AND MATERIALS: We analyzed CNT motion in 65 patients with spinal metastases (11 cervical, 39 thoracic, and 24 lumbar spinal segments) in the supine position using dynamic axial and sagittal magnetic resonance imaging (dMRI, 3T Verio, Siemens) over a 137-second interval. Motion was segregated according to physiologic cardiorespiratory oscillatory motion (characterized by the average root mean square deviation) and random bulk shifts associated with gross patient motion (characterized by the range). Displacement was evaluated in the anteroposterior (AP), lateral (LR), and superior-inferior (SI) directions by use of a correlation coefficient template matching algorithm, with quantification of random motion measure error over 3 separate trials. Statistical significance was defined according to P<.05. RESULTS: In the AP, LR, and SI directions, significant oscillatory motion was observed in 39.2%, 35.1%, and 10.8% of spinal segments, respectively, and significant bulk motions in all cases. The median oscillatory CNT motions in the AP, LR, and SI directions were 0.16 mm, 0.17 mm, and 0.44 mm, respectively, and the maximal statistically significant oscillatory motions were 0.39 mm, 0.41 mm, and 0.77 mm, respectively. The median bulk displacements in the AP, LR, and SI directions were 0.51 mm, 0.59 mm, and 0.66 mm, and the maximal statistically significant displacements were 2.21 mm, 2.87 mm, and 3.90 mm, respectively. In the AP, LR, and SI directions, bulk displacements were greater than 1.5 mm in 5.4%, 9.0%, and 14.9% of spinal segments, respectively. No significant differences in axial motion were observed according to cord level or cauda equina. CONCLUSIONS: Oscillatory CNT motion was observed to be relatively minor. Our results support the importance of controlling bulk patient motion and the practice of applying a planning organ-at-risk margin.

Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study.

While laboratory monitoring is not required in patients treated with apixaban, a direct factor-Xa inhibitor, assessment of its concentration is useful in some critical situations. However, few data are available on its effect on coagulation tests and on the suitability of anti-Xa assays for its quantification. It was the objective of this study to identify laboratory tests suitable for apixaban concentration assessment. Coagulation tests - PT and aPTT- and anti-Xa assays were performed in apixaban-spiked plasma samples. To evaluate the sensitivity of PT and aPTT to apixaban, we conducted a first monocenter part, with a wide range of concentrations (50-1,000 ng/ml), a large panel of reagents (20 reagents), and two coagulometers (STAR®, Stago and ACL TOP®, IL), and a second multicenter part involving 13 laboratories using either a common PT reagent (RecombiPlastin2G®) or the local PT and aPTT reagents. In the multicentre part, five blinded apixaban-spiked plasma samples (0/100/200/400/800 ng/ml - checked by HPLC-MS/MS) were used; apixaban concentrations were measured with three anti-Xa assays, apixaban calibrators and controls (Stago). PT and aPTT tests using a large panel of reagents displayed a low sensitivity to a wide range of apixaban concentrations. The concentrations to double PT ranged from 400 to >1,000 ng/ml with the 10 reagents. With the three anti-Xa assays, inter-laboratory precision and accuracy were below 11% and 12%, respectively. In conclusion, whereas PT and aPTT tests were not sensitive enough to detect apixaban, the three anti-Xa assays tested using lyophilised apixaban calibrators and controls allowed to reliably quantify a wide range of apixaban concentrations.

Monte Carlo dosimetry of high dose rate gynecologic interstitial brachytherapy.

PURPOSE: To assess the dosimetric effects of the presence of the applicator, air pockets in clinical target volume (CTV) and OARs along with tissue heterogeneities using the Monte Carlo (MC) method in high dose rate (HDR) gynecologic interstitial brachytherapy with a Syed-Neblett template. METHODS AND MATERIALS: The CT based dosimetry has been achieved with the Geant4 MC toolkit version 9.2. DICOM-RT files of 38 patients were imported into our own platform for MC simulations. The dose distributions were then compared to those obtained with a conventional TG-43 calculation. RESULTS: Taking account of heterogeneities has effects of the order of 1% on the HDR gynecological dose distributions. However, the exclusion of air pockets and applicator from the DVH calculation can lower the CTV D90 and V100 by as much as 8.7% and 5.0% in comparison with TG-43. Rectum dosimetric indices can also be lowered by approximately 3% compared with TG-43 for most cases. Differences for urethra and bladder are for most cases below 1%. CONCLUSIONS: Exclusion of non-biological material such as air pockets and applicator volume from the CTV is important for both TG-43 and MC calculations. It could be easily implemented and automated in treatment planning systems without affecting computation times.