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OBJECTIVE Infuse bone graft is a widely used osteoinductive adjuvant; however, the simple collagen sponge scaffold used in the implant has minimal inherent osteoinductive properties and poorly controls the delivery of the adsorbed recombinant human bone morphogenetic protein–2 (rhBMP-2). In this study, the authors sought to create a novel bone graft substitute material that overcomes the limitations of Infuse and compare the ability of this material with that of Infuse to facilitate union following spine surgery in a clinically translatable rat model of spinal fusion. METHODS The authors created a polydopamine (PDA)–infused, porous, homogeneously dispersed solid mixture of extracellular matrix and calcium phosphates (BioMim-PDA) and then compared the efficacy of this material directly with Infuse in the setting of different concentrations of rhBMP-2 using a rat model of spinal fusion. Sixty male Sprague Dawley rats were randomly assigned to each of six equal groups: 1) collagen + 0.2 µg rhBMP-2/side, 2) BioMim-PDA + 0.2 µg rhBMP-2/side, 3) collagen + 2.0 µg rhBMP-2/side, 4) BioMim-PDA + 2.0 μg rhBMP-2/side, 5) collagen + 20 µg rhBMP-2/side, and 6) BioMim-PDA + 20 µg rhBMP-2/side. All animals underwent posterolateral intertransverse process fusion at L4–5 using the assigned bone graft. Animals were euthanized 8 weeks postoperatively, and their lumbar spines were analyzed via microcomputed tomography (µCT) and histology. Spinal fusion was defined as continuous bridging bone bilaterally across the fusion site evaluated via µCT. RESULTS The fusion rate was 100% in all groups except group 1 (70%) and group 4 (90%). Use of BioMim-PDA with 0.2 µg rhBMP-2 led to significantly greater results for bone volume (BV), percentage BV, and trabecular number, as well as significantly smaller trabecular separation, compared with the use of the collagen sponge with 2.0 µg rhBMP-2. The same results were observed when the use of BioMim-PDA with 2.0 µg rhBMP-2 was compared with the use of the collagen sponge with 20 µg rhBMP-2. CONCLUSIONS Implantation of rhBMP-2–adsorbed BioMim-PDA scaffolds resulted in BV and bone quality superior to that afforded by treatment with rhBMP-2 concentrations 10-fold higher implanted on a conventional collagen sponge. Using BioMim-PDA (vs a collagen sponge) for rhBMP-2 delivery could significantly lower the amount of rhBMP-2 required for successful bone grafting clinically, improving device safety and decreasing costs.

The present work sought to confirm the factor structure and examine longitudinal strengths-based and mental health correlates of the dysregulation profile (DP) in children of at-risk fragile families of diverse ethnoracial backgrounds. The data came from the Fragile Families and Child Wellbeing Study (N = 2125 families). Mothers (Mage = 25.3) were mostly unmarried (74.6%), and children (51.4% boys) were identified as Black (47.0%), Hispanic (21.4%), White (16.7%), or multiracial or other backgrounds. Childhood DP was constructed using mother reports of the Child Behavior Checklist at age 9. Mothers’ in-home parent–child interactions and depressive symptoms were assessed at child age 5. At age 15, children responded about their own mental health, social skills, and other strengths-focused outcomes. A bifactor DP structure fit well to the data, with the DP factor representing difficulties in self-regulation. Using SEM, we found that mothers who were more depressed and used less warm parenting at child age 5 had children who presented with higher DP at age 9. DP was in turn associated with less social skills, perseverance, optimism, and more anxiety, depression, and impulsivity at adolescence. Childhood DP appears to be relevant and applicable for at-risk, diverse families, and may also impede on children’s future positive functioning.

Fostemsavir, a prodrug of temsavir, is indicated for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection, antiretroviral (ARV) intolerance, or safety considerations. Understanding drug-drug interactions (DDIs) is important in individuals taking fostemsavir with hormonal contraceptives or menopausal or gender-affirming hormonal therapies.Effect of temsavir (active moiety) on the pharmacokinetics of ethinyl estradiol (EE) and norethindrone (NET) was evaluated in an open-label, single-sequence, four-cycle, four-treatment study in 26 healthy female participants (study 206279, NCT02480881). Relevant ARV-contraceptive interaction studies and guideline recommendations were reviewed; that information was then applied to other contraceptive methods and hormone-based therapies to predict the impact of fostemsavir co-administration.Temsavir increased EE concentrations by 40% and had no effect on NET concentrations. Fostemsavir co-administration with hormone therapy is not expected to impact hormone treatment efficacy. Fostemsavir did not impact progestin; therefore, progestin-only and non-hormonal contraceptives will not be impacted by fostemsavir. Recommendations for co-administration of fostemsavir and hormonal contraceptives or menopausal or gender-affirming hormone therapies are based upon known and predicted DDIs, ensuring adequate hormonal concentrations to maintain the target effect.Applying the results of Study 206279 and other relevant ARV-contraceptive studies, we recommend that when co-administering fostemsavir with combined oral contraceptives (COCs) and other oestrogen-based therapies, EE dose should not exceed 30 μg or equivalent, and caution is advised in the case of individuals with risk factors for thromboembolic events. Other oestrogen-based therapies may be co-administered with fostemsavir, with monitoring of oestrogen concentrations and appropriate dose adjustments. No impact of fostemsavir on COC efficacy is expected.

The Interracial Couples’ Life Transitions (ICLT) model proposes that: i) interethnic parents experience more coparenting difficulties upon the birth of a child compared to same-ethnicity parents; and ii) there exists heterogeneity in interethnic parents’ coparenting quality, thus the coparenting experience cannot be generalized across all interethnic unions. In the present work, we examined these two propositions using a large-scale database of elevated risk, fragile families. In Study 1, we compared the longitudinal trajectories of coparenting in interethnic parents ( n = 574 mother-father unions) and their matched same-ethnicity counterparts ( n = 574 each mothers and fathers) and found that interethnic parents of Asian, Black, Hispanic, and White backgrounds consistently experienced lower and decreasing trajectories of coparenting compared to their counterparts across the first 9 years of a child’s life. In Study 2, we examined heterogeneity in coparenting trajectories for only interethnic mothers and fathers ( n = 1148) and found a three-trajectory profile in which the majority (75.5%) of parents fall into a contented (stable and high) coparenting profile. Our findings confirm and extend on the ICLT model, showing that most interethnic parents experience more coparenting difficulties across time compared to their counterparts, and although there is some heterogeneity in interethnic parents’ coparenting trajectories, most interethnic parents appear to experience stable and content coparenting across time.

There is a growing scientific interest regarding the importance of parental autonomy support (AS) in early childhood. The purpose of this chapter is to review studies on this topic, describe how parental AS toward young children (i.e., infants, toddlers, and preschoolers) has been measured, and document what child characteristics and outcomes have been associated with it. The chapter reviews studies whose AS measure was consistent with self-determination theory’s conceptualization and organizes them by the social context in which it was assessed: play, conversation, help provision, and socialization. After describing each study’s procedure, AS operationalization, and main results, the chapter addresses conceptual issues that should be considered in future studies.

Autonomy support (AS), or autonomy-supportive behavior (AS behavior), is a key ingredient of high-quality hierarchical relationships. Yet how parents and other authority figures can support children’s autonomy—that is, their volitional functioning—in various daily situations remains unclear as AS operationalizations have differed across studies. In an effort to further our understanding of AS behaviors, this chapter highlights their common features (i.e., empathic, informational, and supportive of active participation) as well as their variability. It proposes that AS behaviors may have varied across studies because volition is derived from two different processes (i.e., intrinsic motivation and internalization) and that different AS behaviors may be needed to effectively support volitional functioning originating from each of these processes. Guided by Grusec and Davidov’s domains-of-socialization framework, the chapter argues that intrinsic motivation and internalization are likely to operate differently across domains of socialization, which could account for the variability of AS behaviors. Adopting a domain-specific approach to socialization may thus prove useful to clarify how parents can support their children’s volitional functioning across daily socialization challenges.

IntroductionWe investigated whether initial risk classes and heterogeneous trajectories of self-compassion over the course of the pandemic may impact well-being outcomes 1 year into the pandemic.MethodsA large, representative sample of Canadians (N = 3,613; 50.6% women) was sampled longitudinally over 11 waves (April 2020–April 2021), using a rolling cross-sectional survey design. Analyses were conducted in three steps: (1) latent class analysis to identify heterogeneity in risk factors (sociodemographic, cognitive-personality, health-related) early in the pandemic, (2) latent class growth analysis (LCGA) to identify longitudinal self-compassion trajectories, and (3) GLM to examine effects of risk factor classes and self-compassion trajectories, as well as their interaction, on later well-being (mental health, perceived control, life satisfaction).Results and DiscussionFour risk factor classes emerged, with 50.9% of participants experiencing low risk, 14.3% experiencing multiple risks, 20.8% experiencing Cognitive-Personality and Health risks, and 14.0% experiencing sociodemographic and Cognitive-Personality risks. Four self-compassion trajectories also emerged, with 47.7% of participants experiencing moderate-high self-compassion that decreased then stabilized, 32.0% experiencing moderate self-compassion that decreased then stabilized, 17.3% experiencing high and stable self-compassion across time, and 3.0% experiencing low and decreasing self-compassion. Comparisons of well-being outcomes 1 year post-pandemic indicated that higher levels of self-compassion over time may protect against the impact of initial risk on well-being outcomes. Further work is still needed on heterogeneity in experiences of risk and protective factors during stressful life events.

Project title: Anti-SARS-CoV-2 mRNA vaccination among patients living with SLE in Sweden: coverage progression and clinical effectiveness. Protocol authors: Arthur Mageau & Elizabeth V. Arkema Date: 2023-02-09 Updated: 2023-04-18 1. BACKGROUND Patients living with systematic lupus erythematosus (SLE) raise a particular concern in the COVID-19 pandemic in particular because of their immunosuppression and their comorbidities. A previous study showed that SLE was independently associated with a poor prognosis after a COVID-19 associated organ failure (1). Therefore, anti-SARS-CoV-2 vaccination was quickly recommended in the SLE population (2). Unfortunately, several immunological reports showed that the ability of SLE patients to produce a humoral response following vaccination was lower than the general population, even for patients without immunosuppressive treatments (3,4). However, the humoral response measured by the concentration of vaccine-induced anti-Spike (anti-S) antibodies, which has been the most studied, is only a surrogate marker of the vaccine effectiveness. Thus, some studies showed that immunocompromised patients could have a T-cell-driven vaccine response even without a humoral response (5). Unfortunately, real-world data assessing the effectiveness of the vaccination using clinical outcomes in this population are currently lacking. Furthermore, the impact of the different kind of immunosuppression has not been studied at a large scale and with long-term follow-up. A better understanding of the vaccination effectiveness and of the factors associated with a decreased effectiveness could help to improve the vaccination guidelines in this population. 2. RESEARCH QUESTIONS Our overall aim is to determine whether, to which extent and among which patients, anti-SARS-CoV2 mRNA vaccination clinical effectiveness is affected by SLE. Specifically, we aim to answer the following questions: 1- Was the progression of the vaccination coverage similar between SLE patients and general population ? 2- Do vaccinated SLE patients have an increased risk of hospitalization for COVID-19 compared to vaccinated people without SLE from the general population? 3- Among patients living with SLE, does the risk of COVID-19 hospitalization vary by immunosuppressive treatment? 1. METHODS Study design Matched cohort study. Study population We will define two study populations: one for the description of the vaccination coverage (aim 1) and one for the assessment of vaccine effectiveness (aims 2 & 3). Study populations will be comprised of exposed and unexposed individuals, defined below, using information from the nationwide Swedish registers. These registers can be linked using the personal identification number to identify exposure, outcome and other variables. The population will be restricted to individuals ≥ 18 y.o living in Sweden at the start of the vaccination campaign (January 1st 2021). Study population 1: Description of the vaccination coverage progression (aim 1) Exposed individuals: - The exposure is SLE, defined as having two ICD M32 codes (excluding M32.0, drug-induced lupus) with at least 1 specialist visit before January 2021 (also ≥ 18 y.o, living in Sweden as of Jan 2021). Our objective is to include the whole SLE population for this descriptive part. Non-exposed individuals: Ten population controls selected at random from the Total Population Register (TPR) were matched to each unique individual with SLE on year of birth, sex, county of residence and living in Sweden at the time the matched case was first identified with SLE (index date). We will include all the matched controls ≥ 18 y.o living in Sweden at the start of the vaccination campaign (January 1st 2021). Study population 2: Vaccine effectiveness assessment (aims 2 & 3) We will aim to include COVID-19 naïve individuals with and without SLE vaccinated by mRNA vaccines in order to have the most homogeneous exposed group. Exposed individuals: The exposure is prevalent SLE, defined as having two ICD M32 codes (excluding M32.0, drug-induced lupus) with at least 1 specialist visit before January 2021. - Still alive and still living in Sweden at the time of their 2nd vaccine dose - Age ≥ 18 y.o at the time of their 2nd vaccine dose - Who received two-doses of anti-SARS-CoV2 mRNA vaccines in 2021. - Without any COVID-19 diagnosis code in the national patient register before the 2nd vaccine dose. - With more than 10 days and less than 90 days between the two injections. This delay will be defined as an inclusion criterion in order to avoid selecting people with very unusual vaccination scheme that might reflect pre-exposure to SARS-CoV-2 or errors in the register. Non-exposed individuals: Ten population controls selected at random from the Total Population Register (TPR) were matched to each unique individual with SLE on year of birth, sex, county of residence and living in Sweden at the time the matched case was first identified with SLE (index date). Among these controls we will include individuals: - Who received two-doses of anti-SARS-CoV2 mRNA vaccines in 2021 - Still alive and still living in Sweden at the time of their 2nd vaccine dose - Age ≥ 18 y.o at the time of their 2nd vaccine dose - Without any COVID-19 diagnosis code before the 2nd vaccine dose - With more than 10 days and less than 90 days between the two injections Among these patients we will define subpopulations according to the disease-modifying treatments that they received and according to their comorbidities. We will define the use of an oral treatment if a patient had two dispensations of the same drug during the year before inclusion (i.e. January 1st 2021 for vaccination coverage description and date of first dose for vaccine effectiveness assessment). For treatment given by infusion (belimumab, rituximab and cyclophosphamide) we will define the use if a patient had one infusion during the last 6 months before inclusion. .Comorbidities (history of end-stage renal disease, renal transplantation, chronic kidney disease, obesity, diabetes, hypertension…) will be defined using ICD codes, procedures codes and treatments as proxy. Outcomes Aim 1 : The main outcome for aim 1 will be first vaccine injection. The objective is to present an overview of the progression of the vaccination coverage in SLE patients living in Sweden. The progression of the vaccination coverage in the matched general population will be also presented, as a reference. Aim 2 & 3: The main outcome will be a first hospitalization with COVID-19 (defined as ICD-10 codes U07.1 or U07.2) as main diagnosis for the hospitalization. Deaths related to COVID-19 (with U07.1 or U07.2 codes reported as primary or underlying cause of death in the death-register) will be a secondary outcome. In sensitivity analyses, we will change the definition of the primary outcome to include only hospitalization with U07.1 (virus identified) ICD-10 code, with COVID-19 related ICD-10 codes such as dyspnea or sepsis or with ICU admission. Other variables - Age (TPR) - Sex (TPR) - Country of birth (TPR) - Education level (TPR) - Region of living (TPR) - Number of children (TPR) - Civil status (TPR) - Treatment (PDR+NPR). We will define the use of a treatment if a patient had two dispensations of the same drug during the year before inclusion (i.e. January 1st 2021 for vaccination campaign description and date of first dose for vaccine effectiveness assessment). o Immunosuppressants: we will consider the use of mycophenolic acid (ATC code L04AA06), methotrexate (L04AX03), oral corticosteroids (H02AB07), and azathioprine (L04AX01) in the PDR. o Hydroxychloroquine (ATC code P01BA02) in the PDR o For biologics (rituximab [L01FA01], belimumab [L04AA26]) and cyclophosphamide [L01AA01] we will define the use if a patient had one infusion during the last 6 months before inclusion. - Comorbidities (NPR + PDR) will be defined as any history of these and without any time window. o High blood pressure (ICD-code I10) o Chronic kidney disease (ICD-codes N183,N184,N185) o Obesity (ICD code E66) o Diabetes (ICD codes E10,E11,E12,E13,E14,O24 and/or use of antidiabetic drugs (ATC codes beginning with A10). - Time since first SLE diagnosis (NPR) Follow-up For the description of the vaccination coverage, the follow-up period will be the year 2021 (January 1st -December 31st). For vaccine effectiveness assessment, start of follow-up will be defined as the date of the second dose of the anti-SARS-CoV-2 mRNA vaccine. End of follow-up will be the date of the first in-hospital admission for COVID-19, death, emigration, 3rd vaccine dose or 12 months-post time 0, whichever comes first. We will censor individuals at 3rd vaccine dose because our main interest is the clinical effectiveness of the first two doses and because the time between the 2nd and the 3rd dose may vary a lot between patients. We will define a global censoring 12 months after second dose if none of the listed events occurred because we consider that the effect of the vaccine is not supposed to last longer than 12 months (the strains changed, the vaccine was less effective against Omicron, and the immune response would be greatly diminished, if not gone). Statistical Analysis Aim1: To describe the vaccination campaign course, we will calculate and plot a cumulative incidence function using first vaccine injection as outcome of interest and death or emigration as competing events. We will describe the characteristics of the SLE population remaining unvaccinated in September 2021 with simple descriptive statistics and compare them to those SLE patients who get vaccinated. Aim 2: Vaccine effectiveness will be studied with a time-to-event analysis using a marginal Cox proportional hazard model that considers the matching between exposed and non-exposed patients. We will use inverse probability censoring weighted (IPCW) to take the censoring mechanism into account. We will also calculate unadjusted and adjusted incidence rates. The model will be adjusted for age, sex, health administrative region and household composition. Household composition will be defined using a three-level variable : ‘"Living alone" / “"Living with partner, without child"/ "Living with child(ren), with or without partner". This will be derived from civil status and child aged younger than 18. The main result will be the HR associated with SLE diagnosis compared to non-SLE comparators and 95% confidence intervals. Aim 3: We will divide the whole study population in three groups : 1-general population (excluding individuals under immunosuppressive drug), 2-SLE patients without immunosuppressive drug and 3-SLE patients under immunosuppressive treatment. Hydroxychloroquine will not be considered as an immunosuppressive drug. We will plot the survival without COVID-19-related hospitalization in these three groups using Kaplan-Meier method. Then, we will run one/several standard Cox regression model(s) to calculate the hazard ratio associated to SLE with or without immunosuppressive treatment, using general population as reference. We will use main comorbidities and variables listed in aim 2 as covariates. Finally, we will describe more precisely which immunosuppressive drugs are used by patients that experienced the main outcome. Because we will probably have very low numbers of patients in each category, we will not perform any statistical test here. PRELIMINARY RESULTS We have observed that, according to our inclusion criteria, 7 429 SLE patients and 64 568 matched controls were ≥ 18 y.o and living in Sweden at January 1st 2021. Below is plotted the cumulative incidence function of their time to first vaccine dose : 2. ETHICAL APPROVAL Ethics Review Board DNR 2021-01148 3. LIMITATIONS/CHALLENGES/QUESTIONS The COVID ICD-10 codes might not always be accurate. Some patients may have a previous COVID-19 infection without any indication of it in the Patient Register because we do not have testing data nor primary care data. We are capturing ICD codes for COVID-19 from hospital care, which misses less severe infection. It is a strength to examine the more severe outcome, which the vaccine was developed to address. We assumed that the only reason that drove the decision to admit was the immediate severity of the patient, but patients with SLE might be more likely to be hospitalized with COVID-19 than people without SLE (differential misclassification of the outcome). The collection of the immunosuppressive treatment might not reflect the state of immunosuppression at time of vaccination and during the follow-up. We could lack power. Some comorbidities like obesity and diabetes could be badly reported in the register. We have no access to the type different strains of SARS-CoV-2 involved in the COVID-19 episode. 4. TIME PLAN February -March-April 2023: run the analyses April – May 2023: write the manuscript, receive co-author feedback, present results at KEP, submit an abstract to ACR (due June) June 2023: Submission of the manuscript 5. FUNDING AM is funded by a PhD fellowship of the Fondation pour la Recherche Médicale. 6. REFERENCES 1. Mageau A, Papo T, Ruckly S, Strukov A, van Gysel D, Sacre K, et al. Survival after COVID-19-associated organ failure among inpatients with systemic lupus erythematosus in France: a nationwide study. Ann Rheum Dis. avr 2022;81(4):569‑74. 2. Landewé RBM, Kroon FPB, Alunno A, Najm A, Bijlsma JW, Burmester GRR, et al. EULAR recommendations for the management and vaccination of people with rheumatic and musculoskeletal diseases in the context of SARS-CoV-2: the November 2021 update. Ann Rheum Dis. 1 déc 2022;81(12):1628‑39. 3. Mageau A, Ferré VM, Goulenok T, Charpentier C, Delory N, Francois C, et al. Severely impaired humoral response against SARS-CoV-2 variants of concern following two doses of BNT162b2 vaccine in patients with systemic lupus erythematosus (SLE). Ann Rheum Dis. 8 avr 2022;annrheumdis-2022-222498. 4. Moyon Q, Sterlin D, Miyara M, Anna F, Mathian A, Lhote R, et al. BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in systemic lupus erythematosus. Ann Rheum Dis. 4 oct 2021;annrheumdis-2021-221097. 5. Bitoun S, Henry J, Desjardins D, Vauloup-Fellous C, Dib N, Belkhir R, et al. Rituximab Impairs B Cell Response But Not T Cell Response to COVID-19 Vaccine in Autoimmune Diseases. Arthritis Rheumatol [Internet]. [cité 1 avr 2022];n/a(n/a). Disponible sur: http://onlinelibrary.wiley.com/doi/abs/10.1002/art.42058

ObjectiveWe analysed the incidence of, the specific outcomes and factors associated with COVID-19-associated organ failure (AOF) in patients with systemic lupus erythematosus (SLE) in France.MethodsWe performed a cohort study using the French national medical/administrative hospital database for the January 2011–November 2020 period. Each patient with SLE diagnosed in a French hospital with a COVID-19-AOF until November 2020 was randomly matched with five non-SLE patients with COVID-19-AOF. We performed an exact matching procedure taking age ±2 years, gender and comorbidities as matching variables. COVID-19-AOF was defined as the combination of at least one code of COVID-19 diagnosis with one code referring to an organ failure diagnosis.ResultsFrom March to November 2020, 127 380 hospital stays in France matched the definition of COVID-19-AOF, out of which 196 corresponded with patients diagnosed with SLE. Based on the presence of comorbidities, we matched 908 non-SLE patients with COVID-19-AOF with 190 SLE patients with COVID-19-AOF. On day 30, 43 in-hospital deaths (22.6%) occurred in SLE patients with COVID-19-AOF vs 198 (21.8%) in matched non-SLE patients with COVID-19-AOF: HR 0.98 (0.71–1.34). Seventy-five patients in the SLE COVID-19-AOF group and 299 in the matched control group were followed up from day 30 to day 90. During this period, 19 in-hospital deaths occurred in the SLE group (25.3%) vs 46 (15.4%) in the matched control group; the HR associated with death occurring after COVID-19-AOF among patients with SLE was 1.83 (1.05–3.20).ConclusionsCOVID-19-AOF is associated with a poor late-onset prognosis among patients with SLE.

There has been growing interest over the years in examining interethnic unions to explore their unique parenting configurations and associated mixed-ethnicity children’s outcomes. One aspect that determines parenting is how parents perceive and experience their parenting role in relation to one another, to their children, and to society at large. The present review aimed to narratively and systematically synthesize the existing literature on the strengths and challenges that parents experience in interethnic unions about themselves, their partners or co-parents, or their mixed-ethnicity children. A total of 49 studies were identified through a systematic search. Included studies were dissertations and published journal articles that contained qualitative and quantitative findings. Five themes were identified about the interethnic parenting experience: (1) strengths in parenting mixed-ethnicity children, (2) challenges in interethnic parenting, including the specific challenge of negotiating cultural differences between parents, (3) strategies to overcome cultural differences, (4) self-reflections about parents’ own ethnocultural backgrounds, and (5) similarities in parenting between interethnic and non-interethnic parents. A Model of Interethnic Parenting Experiences summarizing the identified themes is outlined. The review findings are discussed with reference to gaps in the literature and potential moderators of the known parameters regarding interethnic parenting. Recommendations for future research are made that may further elucidate the nuanced experience of interethnic parenting.

Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval of thrombopoietin receptor agonists (TPO-RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO-RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicentre retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defined according to international criteria. We included 185 patients, 100 (54.1%) and 135 (73.0%) patients had received TPO-RAs and/or rituximab before the splenectomy. The median follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) patients had an initial response and 23 (12.4%) experienced relapse during follow-up, for an overall sustained response of 65.4%, similar to that observed in the pre-TPO-RA era. Among patients who received at least one TPO-RA or rituximab before splenectomy, 92/151 (60.9%) had a sustained response. Six of 13 (46%) patients with previous lack of response to both TPO-RAs and rituximab had a sustained response to splenectomy. Among patients with relapse after splenectomy, 13/21 (61.2%) patients responded to one TPO-Ras that failed before splenectomy. In conclusion, splenectomy is still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients with lack of response or with relapse after splenectomy should be re-challenged with TPO-RAs. This article is protected by copyright. All rights reserved.

Quality indicators (QIs) for systemic lupus erythematosus (SLE) management based on the 2019 update of European League Against Rheumatism (EULAR) recommendations have been recently proposed. We aimed to determine whether adherence to QIs was associated with patient reported outcome (PRO).Adherence to a set of 18 EULAR-based QIs and correlation with PRO assessed by Lupus Impact Tracker (LIT) was tested in a cohort of 162 SLE patients.On average, SLE patients received 41% (33; 52.5) of recommended care. Higher adherence to monitoring-related QIs was associated with an older age, a shorter SLE disease duration and a more severe disease (i.e. Class III/IV/V nephritis). LIT demonstrated that the average impact of lupus on patients' life was of 30% (12.5;47.5). In multivariable analysis, patients of female gender (OR 0.25, 95% 0.05-0.94; p = 0.05), with lupus CNS (OR 0.33, 95%CI 0.08-1.05; p = 0.08) and skin involvements (OR 0.49, 95%CI 0.23-1.04; p = 0.07) had higher odds of experiencing a negative impact of the lupus on their life. No association were found between adherences to QIs by physicians and reported quality of life in lupus patients.Our study confirms a variable degree of clinicians' adherence to QIs for SLE and shows no clear association between QIs adherence and patient reported outcome. Adherence to QIs by physicians are not enough to impact the quality of life of patients.

PURPOSE Adipose distribution and sarcopenia could better assess kidney transplantation outcomes than body mass index (BMI) and have been poorly evaluated among obese and overweight recipients. We aimed to evaluate morphometric radiologic markers to predict post-operative dialysis within this population. METHODS We conducted a retrospective study including patients with a BMI > 25 kg/m2 undergoing kidney transplantation during 5 years. Subcutaneous adipose tissue surface (SAT), visceral adipose tissue surface (VAT), and psoas surface were measured on CT scans sections. A model predictive of post-transplantation dialysis was elaborated through a multivariable logistic regression and was compared to a model including only BMI. RESULTS Overall, 248 patients were included whom mean (SD) BMI and age were, respectively, 29.7 kg/m2 (3.6) and 56 years (12.7). Of them, 83 (33.5%) needed dialysis: 14 (5.7%) for primary kidney failure and 69 (27.8%) for delayed kidney function. On multivariable analysis, SAT, VAT and deceased donor were significantly associated with post-operative dialysis (respectively, OR [95%CI]:1.6 [1.1-2.6], 1.6[1.1-2.6], and 7.5 [1.6-56]). The area under the curve of this predictive model was 0.70 versus 0.64 for a BMI-based model. CONCLUSION High VAT and SAT were associated with post-transplantation dialysis. A predictive model based on these morphometrics could provide a better appreciation of graft recovery after transplantation among obese and overweight recipients. External validation is needed.

Sedentary lifestyle is an important public health issue. To prevent this problem, major health organizations promote the inclusion of physical activity in daily life. Active modes are therefore a well-known way of achieving the health recommendations but walking to transit has also been studied recently. The goal of this study is to assess the level of physical activity achieved by using transit, to verify its contribution in reaching the recommendations. The paper aims to assess the energy expenditure associated with transit use by analyzing the related Metabolic Equivalent of Task. This allows us to express trips as physical activity expenditures and to integrate them in the daily pool of physical activities. For this study, only the main variables affecting the intensity of physical activity are considered. These are the walking time and slope encountered during the walking portion of transit trips. This estimation allows us to estimate the level of physical activity reached by transit users and assess the potential physical activity drivers could achieve if they switched to transit. Finally, the method is also applied to a current transportation issue in Montreal. Results show that transit users living in the Montreal area can achieve 54% of their recommended daily physical activity just by using transit. Current users of motorized modes, if they were to change to transit for their daily travels, could achieve 85% of the recommended daily physical activity.

Background Reliable and interpretable automatic extraction of clinical phenotypes from large electronic medical record databases remains a challenge, especially in a language other than English. Objective We aimed to provide an automated end-to-end extraction of cohorts of similar patients from electronic health records for systemic diseases. Methods Our multistep algorithm includes a named-entity recognition step, a multilabel classification using medical subject headings ontology, and the computation of patient similarity. A selection of cohorts of similar patients on a priori annotated phenotypes was performed. Six phenotypes were selected for their clinical significance: P1, osteoporosis; P2, nephritis in systemic erythematosus lupus; P3, interstitial lung disease in systemic sclerosis; P4, lung infection; P5, obstetric antiphospholipid syndrome; and P6, Takayasu arteritis. We used a training set of 151 clinical notes and an independent validation set of 256 clinical notes, with annotated phenotypes, both extracted from the Assistance Publique-Hôpitaux de Paris data warehouse. We evaluated the precision of the 3 patients closest to the index patient for each phenotype with precision-at-3 and recall and average precision. Results For P1-P4, the precision-at-3 ranged from 0.85 (95% CI 0.75-0.95) to 0.99 (95% CI 0.98-1), the recall ranged from 0.53 (95% CI 0.50-0.55) to 0.83 (95% CI 0.81-0.84), and the average precision ranged from 0.58 (95% CI 0.54-0.62) to 0.88 (95% CI 0.85-0.90). P5-P6 phenotypes could not be analyzed due to the limited number of phenotypes. Conclusions Using a method close to clinical reasoning, we built a scalable and interpretable end-to-end algorithm for extracting cohorts of similar patients.

BACKGROUND Reliable and interpretable automatic extraction of clinical phenotypes from large electronic medical records databases remains a challenge, especially in a language other than English. OBJECTIVE We aimed to provide an automated end-to-end extraction of cohorts of similar patients from electronic health records for systemic diseases. METHODS Our multistep algorithm includes a named-entity recognition step, a multilabel classification using Medical Subject Headings ontology and the computation of patient similarity. A selection of cohorts of similar patients on a priori annotated phenotypes was performed. Six phenotypes were selected for their clinical significance: P1-osteoporosis, P2-nephritis in systemic erythematosus lupus, P3-interstitial lung disease in systemic sclerosis, P4-lung infection, P5-obstetric antiphospholipid syndrome, and P6-Takayasu stroke. We used a training set of 151 clinical notes and an independent validation set of 256 clinical notes, with annotated phenotypes, both extracted from the Assistance Publique-Hôpitaux de Paris data warehouse. We evaluated the precision of the 3 patients closest to the index patient for each phenotype with the precision-at-3, and the recall and average precision. RESULTS For P1-P4, the precision-at-3 ranged from 0.85 [0.75, 0.95] to 0.99 [0.98, 1], the recall ranged from 0.53[0.50, 0.55] to 0.83[0.81, 0.84], and the average precision ranged from 0.58 [0.54, 0.62] to 0.88 [0.85, 0.90], respectively. P5-P6 phenotypes could not be analysed due to a limited number of phenotypes. CONCLUSIONS Using a method close to clinical reasoning, we built a scalable and interpretable end-to-end algorithm to extract cohorts of similar patients.

Using structural equation modeling (SEM), this study examines how adolescents’ rated importance (talk) and enactment (walk) of extrinsic values (wealth, beauty, and fame) and intrinsic values (affiliation, self-acceptance, and community) relate to their well-being and risk-taking. An online questionnaire was filled out by 647 adolescents (57.1% girls), aged between 14 and 17 years old (Mage = 15.5 years). Talk intrinsic values were positively associated with well-being, whereas talk extrinsic values were non-significantly related to it. As for the walk measures, we found an interaction between extrinsic and intrinsic values in the prediction of well-being. Extrinsic values enactment and well-being were positively related among adolescents reporting lower intrinsic values enactment, but not among adolescents who reported higher intrinsic values enactment. Finally, using either talk or walk measures, only extrinsic values were associated with higher risk-taking behaviors.

There is an increased risk of osteoporosis and an abnormal bone turn over in neurofibromatosis 1 (NF1). Our objective is to evaluate bone status in NF1 and to look for associations with cutaneous phenotype. We conducted a descriptive, monocentric study. We included 60 NF1 women, 18–51 years old, non-menopausal, divided in 2 groups: «at risk phenotype» (ARP) composed by 30 patients with at least 2 subcutaneous neurofibromas (SC-NF) and «classical phenotype» (CP) composed by 30 patients with none or 1 SC-NF. We evaluated low bone mineral density (BMD) risk factors and measured BMD, calcium and phosphorus homeostasis and bone turnover markers. Before 50 years old, Z-score has to be used to assess BMD. Z-score

Past studies looking at antecedents of controlling parenting revealed an association between parents' use of these detrimental practices and their perceptions of the environment as threatening for their children. However, the causal impact of environmental threats on controlling practices remained to be assessed. This study filled this gap using an experimental design and a sample of 101 children (Mage = 10.21 years) and their mothers. We manipulated mothers' perceptions of environmental threats, subsequently asked them to help their children complete a task in a guided learning setting, and obtained multi-informant observational measures of maternal controlling practices during this interaction. Results first showed that mothers with a high (but not low) controlling style were coded by an independent observer as significantly more controlling in the threat condition than in the control condition. Results also revealed that mothers in the threat condition were perceived by their children as significantly more controlling than mothers in the control condition, regardless of their controlling style. Path analyses then showed that coded maternal practices predicted children's perceptions of maternal controlling practices, which in turn were associated with higher levels of controlled motivation in children. Examining indirect effects also revealed a significant link from environmental threats to children's controlled motivation, via perceived maternal controlling practices. Contributions of these results to the literature on parenting are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The present study examined how toddler temperament (negative affectivity, effortful control, and surgency) and parent stress relate to parents’ use of autonomy support (AS) when making requests. Based on past studies pointing to parent stress and toddler difficult temperament as possible risk factors, we proposed a mediation model where toddler temperament was expected to be related indirectly to parents’ use of autonomy-supportive practices via parent stress. Parents (N = 181) reported how often they used autonomy-supportive practices when asking their toddlers (Mage = 27.7 months) to engage in important, yet uninteresting activities. They also answered questions regarding their toddler’s temperament and their own stress levels. A complete mediation hypothesis was supported for negative affectivity but not for the other temperament dimensions. Both toddler negative affectivity and effortful control were indirectly related to parents’ AS, via parent stress. However, effortful control was also directly associated with parent AS over and above parent stress, while surgency was not related to parent stress or parent AS. The present findings underline the need for more research on how to mitigate the impact of difficult temperamental characteristics so as to preserve parents’ support for their toddlers’ need for autonomy.

Objective: We aimed to provide an automated end-to-end extraction of cohorts of similar patients from electronic health records for systemic diseases. Materials and Methods: Our multistep algorithm includes a named-entity recognition step, a multilabel classification using Medical Subject Headings ontology and the computation of patient similarity. A selection of cohorts of similar patients on a priori annotated phenotypes was performed. Six phenotypes were selected for their clinical significance: P1-osteoporosis, P2-nephritis in systemic erythematosus lupus, P3-interstitial lung disease in systemic sclerosis, P4-lung infection, P5-obstetric antiphospholipid syndrome, and P6-Takayasu stroke. We used a training set of 151 clinical notes and an independent validation set of 256 clinical notes, with annotated phenotypes, both extracted from the Assistance Publique-Hôpitaux de Paris data warehouse. We evaluated the precision of the 3 patients closest to the index patient for each phenotype with the precision-at-3, and the recall and average precision. Results: For P1-P4, the precision-at-3 ranged from 0.85 to 0.99, the recall ranged from 0.53 to 0.83, and the average precision ranged from 0.58 to 0.88, respectively. P5-P6 phenotypes could not be analysed due to a limited number of phenotypes. Conclusion: Using a method close to clinical reasoning, we built a scalable and interpretable end-to-end algorithm to extract cohorts of similar patients.

IFNα and anti-IFNα autoantibodies have been implicated in susceptibility both for systemic lupus erythematosus (SLE) and viral infection. We aimed to analyze the SLE disease phenotype and risk for infection associated with anti-IFN-α IgG autoantibodies in SLE patients In this multidisciplinary retrospective single referral center study, all consecutive patients with SLE admitted between January 1st and November 30th 2020 were considered. All subjects fulfilled the ACR/EULAR 2019 criteria for SLE. Anti-IFNα IgG autoantibodies were quantified at admission by ELISA. Demographic, medical history, laboratory, treatment, and outcome data were extracted from electronic medical records using a standardized data collection form. 180 patients [female 87.2%, median age of 44.4 (34–54.2) years] were included. The median disease duration was 10 years [4–20] with a median SLEDAI score of 2 [0–4] at study time. Fifty-four (30%) patients had a past-history of lupus nephritis. One hundred and forty-four (80%) had received long-term glucocorticoids and 99 (55%) immunosuppressive drugs. Overall, 127 infections—mostly bacterial and viral—were reported in 95 (52.8%) patients. Twenty SLE patients (11.1%) had positive anti-IFNα IgG autoantibodies with a titer ranging from 10 to 103 UA/mL. Age, sex, SLE phenotype and treatment did not significantly differ between SLE patients with or without anti-IFNα. Infection rate was similar in both groups except for tuberculosis which was more frequent in patients with anti-IFNα (20% vs. 3.1%, p = 0.01). The prevalence of autoantibodies against IFNα is high in SLE and associated with a higher frequency of tuberculosis.

International audience; Background and objective: Data regarding interstitial lung disease (ILD) in the setting of systemic lupus erythematosus (SLE) are limited. We used a nationwide database to determine the incidence and the prevalence of ILD in SLE. Methods: Characteristics of all SLE inpatients admitted between 2011 and 2012 in France were analysed through the French medico-administrative database. Features associated with the presence of ILD were studied. Cox hazard model was used to measure the impact of ILD on survival from the first stay to 2020. The incidence of ILD in SLE was estimated by analysing the onset of ILD from 2013 to 2020 in SLE patients who had no evidence of ILD in 2013. Results: Between 2011 and 2012, 10,460 SLE patients had at least one hospital stay and could be traced until 2020. Among them, 134 (1.2%) had an ILD diagnosed at baseline. The frequency of ILD in SLE was higher in patients who had an associated autoimmune disease such as Sjögren's syndrome or systemic sclerosis (29.9% vs. 5.9%, p < 0.0001). ILD was associated with an increased risk of death in SLE in the multivariable analysis (hazard ratio [95% CI] 1.992 [1.420–2.794]; p < 0.0001). Among the 31,029 SLE patients with no evidence of ILD at baseline, ILD occurred in 795 (2.6%) between 2013 and 2020. The incidence rate of ILD in SLE was 10.26 for 1000 patient-years [95% CI: 10.24–10.28]. Conclusion: In SLE, ILD is exceedingly rare, often associated with another systemic autoimmune disorder and appears as a major risk factor for death. © 2022 Asian Pacific Society of Respirology.

Creativity is a highly sought after and multifaceted skill. Unfortunately, we only have a loose grasp on its cognitive underpinnings. Empirical research typically probes creativity by estimating the potential for problem solving and novel idea generation, a process known as “divergent thinking”. Here, by contrast, we examine creativity through the lens of perceptual abilities. In particular, we ask whether creative individuals are better at perceiving recognizable forms in noisy or ambiguous stimuli, a phenomenon known as pareidolia. To this end, we designed a visual perception task in which 50 participants, with various levels of creativity, were presented with ambiguous stimuli and asked to identify as many recognizable forms as possible. The stimuli consisted of cloud-like images with various levels of complexity, which we controlled by manipulating fractal dimension (FD) and contrast level. We found that pareidolic perceptions arise more often and more rapidly in individuals that are more creative. Furthermore, the emergence of pareidolia in individuals with lower creativity scores was more restricted to images with a narrow range of FD values, suggesting a wider repertoire for perceptual abilities in creative individuals. Our findings suggest that pareidolia may be used as a perceptual proxy of idea generation abilities, a key component of creative behavior. In sum, we extend the established body of work on divergent thinking, by introducing divergent perception as a complementary manifestation of the creative mind. These findings expand our understanding of the perception-creation link and open new paths in studying creative behavior in humans.

In society and its mass media, adolescence is typically portrayed as a disruptive and rebellious stage of life ("Storm and Stress"). Previous research suggests that the parental adherence to these negative Storm and Stress beliefs about adolescence are persistent and predict subsequent "Storm and Stress" behaviours among their adolescent children. However, the way these beliefs may impact parenting and the experience of being a parent remains unclear and understudied. This study examined associations between parents' Storm and Stress beliefs about adolescence and parental burnout as well as explored the potential mediating role of parental overprotection in this association. Using an Actor-Partner Interdependence Partial Mediation Model, we examined these associations in 146 mother-father dyads (N = 292 parents) of adolescents. Results indicated that mothers and fathers who adhered more strongly to Storm and Stress beliefs about adolescence were more likely to exhibit higher levels of parental burnout. These associations were partially mediated by parental overprotection for both mothers and fathers. The strength of these pathways were found to be similar for both mothers and fathers and no partner effect was observed. These results suggest that countering negative beliefs about adolescence may be beneficial for the quality of parenting and the experience of being a parent.

To evaluate the specific response of SLE patients to BNT162b2 vaccination and its impact on autoimmunity defined as in vivo production of interferon-alpha (IFNα) by plasmacytoid dendritic cells (pDCs) and autoreactive immune responses.Our prospective study included SLE patients and healthy volunteers (HV) who received 2 doses of BNT162b2 vaccine 4 weeks apart. Subjects under immunosuppressive drugs or with evidence of prior COVID-19 were excluded. IgG anti-Spike SARS-CoV-2 (anti-S) antibodies, anti-S specific-B cells, anti-S specific T cells, in vivo INF-α production by pDCs, activation marker expression by pDCs and autoreactive anti-nuclear T cells were quantified before first injection, before second injection, and 3 and 6 months after first injection.Vaccinated SLE patients produced significantly lower IgG antibodies and specific B cells against SARS-CoV-2 as compared to HV. In contrast, anti-S T cell response did not significantly differ between SLE patients and HV. Following vaccination, the surface expression of HLA-DR and CD86 and the in vivo production of IFNα by pDCs significantly increased in SLE patients. The boosted expression of HLA-DR on pDCs induced by BNT162b2 vaccine correlated with the overall immune responses against SARS-CoV-2 (anti-S antibodies: r = 0.27 [0.05-0.46], p = 0.02; anti-S B cells: r = 0.19 [-0.03-0.39], p = 0.09); anti-S T cells: r = 0.28 [0.05-0.47], p = 0.016). Eventually, anti-SARS-CoV-2 vaccination was associated with an overall decrease of autoreactive T cells (slope = - 0.00067, p = 0.015).BNT162b2 vaccine induces a transient in vivo activation of pDCs in SLE that contributes to the immune responses against SARS-CoV-2. Unexpectedly BNT162b2 vaccine also dampens the pool of circulating autoreactive T cells, suggesting that vaccination may have a beneficial impact on SLE disease.

This chapter explores how self-determination theory (SDT; Ryan & Deci, 2000, 2017), an empirical theory about human motivation and personality, aligns with principles and practices of social and emotional learning (SEL) within the school context. Through its emphasis on basic psychological needs (BPN) for autonomy, competence, and relatedness, SDT proposes a broad perspective on how the social context can facilitate the development of social and emotional skills, which complements SEL programs. Research anchored in SDT has indeed established that students' academic, social, and emotional skills are determined at least partly by the extent to which their BPN are fulfilled in their learning environment. SDT also brings attention to the motivation and goals underlying the teaching and learning of social and emotional skills. Although SDT-based interventions mainly target the school or the classroom climate rather than students' skills, they can also foster the development of the five core social and emotional competencies defined by CASEL (2005). Implications and future directions for practices and research integrating SDT-based principles and interventions within SEL programs and practices are discussed.

Minipigs are an emerging nonrodent alternative for ocular toxicology owing to anatomical similarities in the minipig eyes when compared to humans. Ocular structures and components from Göttingen minipigs were characterized and compared to species commonly used in toxicology. Ocular reference data from Göttingen minipig including intraocular pressure, vitreous electrolyte and thiol concentration, and electroretinography (ERG) data are essential to model characterization and data interpretation during drug safety assessments. Intravitreal positive control agents including gentamicin, indocyanine green, and glycine were used to demonstrate ERG alterations caused by retinal cell toxicity, light transmission obstruction, or neurotransmission interferences, respectively. Electrolyte concentrations of the aqueous and vitreous humors from Göttingen minipigs were similar to other species including humans. The reference data presented herein supports the use of the Göttingen minipig as an alternate nonrodent species in ocular toxicology.