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Abstract Differences in the clinical course and treatment responses in individual patients with advanced renal cell carcinoma (RCC) can largely be explained by the different genomics of this disease. To improve the personalized treatment strategy and survival outcomes for patients with advanced RCC, the genomic make-up in patients with advanced RCC was investigated to identify putative actionable variants and signatures. In this prospective multicenter study (NCT01855477), whole-genome sequencing (WGS) data of locally advanced and metastatic tissue biopsies and matched whole-blood samples were collected from 91 patients with histopathologically confirmed RCC. WGS data were analyzed for small somatic variants, copy-number alterations and structural variants. For a subgroup of patients, RNA sequencing (RNA-Seq) data could be analyzed. RNA-Seq data were clustered on immunogenic and angiogenic gene expression patterns according to a previously developed angio-immunogenic gene signature. In all patients with papillary and clear cell RCC, putative actionable drug targets were detected by WGS, of which 94% were on-label available. RNA-Seq data of clear cell and papillary RCC were clustered using a previously developed angio-immunogenic gene signature. Analyses of driver mutations and RNA-Seq data revealed clear differences among different RCC subtypes, showing the added value of WGS and RNA-Seq over clinicopathological data. By improving both histological subtyping and the selection of treatment according to actionable targets and immune signatures, WGS and RNA-Seq may improve therapeutic decision making for most patients with advanced RCC, including patients with non-clear cell RCC for whom no standard treatment is available to data. Prospective clinical trials are needed to evaluate the impact of genomic and transcriptomic diagnostics on survival outcome for advanced RCC patients.

ObjectiveDescribe the trends of exposure to harmful drugs during pregnancy over recent years in France.DesignNationwide cohort study.SettingThe French National administrative health Data System (SNDS).PopulationPregnancies starting between 2013 and 2019 and outcomes corresponding to live births, medical terminations of pregnancy, and stillbirths.MethodsEach pregnancy was divided into a preconceptional period of 90 days before conception and three trimesters from conception to birth. Harmful drugs were defined according to their risks to the fetus: teratogenicity or fetotoxicity. Exposure was defined using the critical period during pregnancy for each type of harmful drug: preconceptional period or first trimester for teratogenic drugs and second or third trimesters for fetotoxic drugs.Main outcome measuresPrevalence of pregnancies exposed to at least one harmful drug.ResultsAmong 5,253,284 pregnancies, 204,402 (389 per 10,000) pregnancies were exposed to at least one harmful drug during the critical periods: 48,326 (92 per 10,000) pregnancies were exposed to teratogenic drugs during the preconceptional period or the first trimester, and 155,514 (299 per 10,000) pregnancies were exposed to fetotoxic drugs during the second or third trimesters. Teratogenic drugs were mainly retinoids for topical use (44 per 10,000 pregnancies), antiepileptics (13 per 10,000 pregnancies) and statins (13 per 10,000 pregnancies). Fetotoxic drugs were mainly non-steroidal anti-inflammatory drugs (NSAIDs), for systemic (128 per 10,000 pregnancies) and topical use (122 per 10,000 pregnancies). Exposure to teratogenic drugs decreased from the preconceptional period to the first trimester. Exposure to fetotoxic drugs decreased from the second to the third trimester. Between 2013 and 2019, we found a decrease in harmful drug exposure overall, mainly for topical and systemic NSAIDs and for topical retinoids.ConclusionsIn this nationwide study, about one in 25 pregnancies was exposed to at least one harmful drug, mainly NSAIDs and topical retinoids. Although the prevalence of harmful drug exposure decreased over the study period, NSAID exposure in the second and third trimester remains of concern.

Background: Prior research suggests that psychiatric disorders could be linked to increased mortality among patients with COVID-19. However, whether all or specific psychiatric disorders are intrinsic risk factors of death in COVID-19 or whether these associations reflect the greater prevalence of medical risk factors in people with psychiatric disorders has yet to be evaluated. Methods: We performed an observational, multicenter, retrospective cohort study to examine the association between psychiatric disorders and mortality among patients hospitalized for laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals. Results: Of 15,168 adult patients, 857 (5.7%) had an ICD-10 diagnosis of psychiatric disorder. Over a mean follow-up period of 14.6 days (SD = 17.9), 326 of 857 (38.0%) patients with a diagnosis of psychiatric disorder died compared with 1276 of 14,311 (8.9%) patients without such a diagnosis (odds ratio 6.27, 95% CI 5.40–7.28, p < .01). When adjusting for age, sex, hospital, current smoking status, and medications according to compassionate use or as part of a clinical trial, this association remained significant (adjusted odds ratio 3.27, 95% CI 2.78–3.85, p < .01). However, additional adjustments for obesity and number of medical conditions resulted in a nonsignificant association (adjusted odds ratio 1.02, 95% CI 0.84–1.23, p = .86). Exploratory analyses after the same adjustments suggested that a diagnosis of mood disorders was significantly associated with reduced mortality, which might be explained by the use of antidepressants. Conclusions: These findings suggest that the increased risk of COVID-19–related mortality in individuals with psychiatric disorders hospitalized for COVID-19 might be explained by the greater number of medical conditions and the higher prevalence of obesity in this population and not by the underlying psychiatric disease.

Abstract The acid sphingomyelinase (ASM)/ceramide system may provide a useful framework for better understanding SARS-CoV-2 infection and the repurposing of psychotropic medications functionally inhibiting the acid sphingomyelinase/ceramide system (named FIASMA psychotropic medications) against COVID-19. We examined the potential usefulness of FIASMA psychotropic medications in patients with psychiatric disorders hospitalized for severe COVID-19, in an observational multicenter study conducted at Greater Paris University hospitals. Of 545 adult inpatients, 164 (30.1%) received a FIASMA psychotropic medication upon hospital admission for COVID-19. We compared the composite endpoint of intubation or death between patients who received a psychotropic FIASMA medication at baseline and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, psychiatric and other medical comorbidity, and other medications. FIASMA psychotropic medication use at baseline was significantly associated with reduced risk of intubation or death in both crude (HR = 0.42; 95%CI = 0.31–0.57; p

When discussed in the context of diagnosing or medicating children, psychiatrization is usually portrayed as a more or less monolithic top-down process, which, according to some, enables a child's right to health, while for others is a form of child abuse. This article challenges these conceptualizations in two steps: First, it draws on available literature on psychiatrization (including its top-down and bottom-up operations, and its ideological and material aspects), and its relationship to various psy-practices, and wider processes of (bio) medicalization, psychologization and reification. Second, using two detailed vignettes from ethnographic research with children and youth in Poland, the article demonstrates that children and youth are not necessarily passive recipients of psychiatrization as they themselves navigate, appropriate, resist, and transform top-down influences. While one vignette details a child's more or less open resistance to psychiatrization through their attention-deficit/hyperactivity disorder label, the other vignette shows young people embracing and positively identifying with bio and psy-knowledge in relation to depression. However, both vignettes show how children and youth make psychiatrization meaningful as it shapes their lifeworlds, with them sometimes becoming agents of psychiatrization themselves. Our data illustrate the nuances of psychiatrization of, with and by children, and we draw on this to complexify existing literature and framings of psychiatrization.

BackgroundThe clinical characteristics, disease progression and outcome in children affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appear significantly milder compared to older individuals. Nevertheless, the trends in hospitalization and clinical characteristics in the pediatric population seem to be different over time across the different epidemic waves.ObjectiveOur aim was to understand the impact of the different COVID-19 variants in the pediatric population hospitalized in the Pediatric Departments of the Public Hospital in the Greater Paris area by the analysis performed with the Assistance Publique-Hopitaux de Paris (AP-HP) Health Data Warehouse.MethodsThis is a retrospective cohort study including 9,163 patients under 18 years of age, hospitalized from 1 March 2020 to 22 March 2022, in the Paris area, with confirmed infection by SARS-CoV-2. Three mutually exclusive groups with decreasing severity (Pediatric Inflammatory Multisystem Syndrome (PIMS), symptomatic infection, mild or asymptomatic infection) were defined and described regarding demography, medical history, complication of the SARS-CoV-2 infection, and treatment during admission. Temporal evolution was described by defining three successive waves (March–September 2020, October 2020–October 2021, and November 2021–March 2022) corresponding to the emergence of the successive variants.ResultsIn the study period, 9,163 pediatric patients with SARS-CoV-2 infection were hospitalized in 21 AP-HP hospitals. The number of patients with SARS-CoV-2 infection increased over time for each wave of the pandemic (the mean number of patients per month during the first wave was 332, 322 during the 2nd, and 595 during the third wave). In the medical history, the most associated concomitant disease was chronic respiratory disease. Patients hospitalized during the third wave presented a higher incidence of pulmonary involvement (10.2% compared to 7% and 6.5% during the first and second waves, respectively). The highest incidence of PIMS was observed during the first and second waves (4.2% in the first and second waves compared to 2.3% in the 3rd wave).DiscussionThis analysis highlighted the high incidence of hospitalized children in the Greater Paris Area during the third wave of SARS-CoV-2 pandemic corresponding to the Omicron Covid-19 variant, which is probably an expression of a concomitant SARS-CoV-2, while a decreased incidence of PIMS complication was observed during the same period.

BackgroundIn the light of high incidences of diagnosed mental disorders and the growing utilization of mental healthcare services, a progressing psychiatrization of society has been hypothesized as the underlying dynamic of these developments. Mental healthcare institutions, such as psychiatric hospitals, may play a decisive role in this. However, there is a scarcity of research into how psychiatrization emerges in hospital settings. This paper explores whether the emergency department (ED) can be considered as a site where psychiatrization happens, becomes observable, and which factors in the context of the ED may be its potential drivers.MethodsTwo cases as encountered in an interdisciplinary ED will be presented in the following in an anonymized way. Although the cases originate from individual consultations, they can be considered as prototypical. The cases were collected and discussed using the method of interactive interviewing. The results will be analyzed against the backdrop of current theoretic concepts of psychiatrization.FindingsThe ED can be seen as an important area of contact between society and psychiatry. Decisions whether to label a certain condition as a “mental disorder” and to therefore initiate psychiatric treatment, or not, can be highly difficult, especially in cases where the (health) concerns are rather moderate, and clearly associated with common life problems. Psychiatrists' decisions may be largely influenced in favor of psychiatrization by a wide array of disciplinary, institutional, interpersonal, personal, cultural, and social factors.ConclusionsThe ED appears to be a promising field for research into the mechanisms and motives through which psychiatrization may emerge in mental healthcare settings. Psychiatrists in the ED work within a complex sphere of top-down and bottom-up drivers of psychiatrization. Encounters in the ED can be an important step toward adequate support for many individuals, but they also risk becoming the starting point of psychiatrization by interpreting certain problems through the psychiatric gaze, which may induce diagnoses of questionable validity and treatment of little use.