Factors associated with the decision of a French hospital to report child abuse to judicial rather than administrative authorities

ObjectivesTwo independent sectors manage the child protection system in France: judicial and administrative protection. The choice between judicial or administrative reporting depends on the seriousness of the case. The goal of this study was to determine the characteristics associated with the decision in a French pediatric hospital to report child abuse to judicial instead of administrative authorities.MethodsA retrospective study was conducted. Participants were all the children (n = 83) who were admitted from 2017 to 2018 to the emergency department (ED) and the general ward of a pediatric university hospital in France, and were reported for suspicion of child abuse by the professional teams. The children who were suspected victims of sexual abuse were excluded. Multivariate logistic regressions were used.ResultsA total of 47 children were reported to judicial authorities, and 36 to administrative authorities. Their median age was 7 years. Suspicion of physical abuse (odds ratio [OR]: 21.2; 95% confidence interval [CI]: 4.5–99.1), cases reported by the pediatric ward team (OR: 9.1; 95% CI: 1.9–43.6), adult person different from parents who accompanied the child to the ED (OR: 5.8; 95% CI: 1.2–28.6), and perception of parental behavior as inappropriate and non-cooperative (OR: 6.6; 95% CI: 1.4–29.6) were associated with a higher risk of the case being reported to judicial authorities. Data were often unavailable for parental health issues, history of child abuse, and intimate partner violence.ConclusionSome factors associated with the choice of report type were most likely quite subjective. Better documentation and standardization are needed.     

Upon Drug-Induced Apoptosis Expression of Prostate-apoptosis-response-gene-4 Promotes Cleavage of Caspase-8, Bid and Mitochondrial Release of Cytochrome c

Par-4 functions as a tumor suppressor antagonizing the transforming capacity and the resistance of malignant cells towards apoptotic stimuli. After demonstrating that par-4 promotes apoptosis by activating signaling of the intrinsic pathway of apoptosis, we hypothesized that par-4 also impacts on key molecules of the extrinsic pathway without the requirement of a receptor/ligand interaction. Here, we provide first evidence, that expression of par-4 increases cleavage of caspase-8, truncation of Bid and its translocation to the mitochondria, resulting in an augmentation of cytochrome c and AIF efflux into the cytosol, effects par-4-positive cells are able to retain to a higher extent than par-4-negative cells upon inhibition of caspase-3 activation.     

Clinical stakeholders’ opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units: an international Delphi study

Introduction

Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic regimen that is not widely used in practice. We aimed to describe the opinions of key ‘stakeholders’ about the validity of the existing evidence base, likely consequences of implementation, relative importance of their opinions in influencing overall practice, likely barriers to implementation and perceptions of the requirement for further research to inform the decision about whether to embark on a further large randomised controlled trial.

Methods

This was a Delphi study informed by comprehensive framework of possible determinants of health professionals’ behaviour to study Critical Care practice in four countries. There were four key stakeholder participant groups including ICU physicians, pharmacists, clinical leads, and clinical microbiologists/ infectious disease physicians. Round one comprised participant interviews and Rounds two and three were online questionnaires using Delphi method.

Results

In this study, 141 participants were recruited of whom 82% were retained. Participants rated themselves as knowledgeable about SDD. Antibiotic resistance was identified as the most important issue. SDD was seen as a low clinical priority but few participants reported strong opposition. There was moderate agreement that research to date has not adequately addressed concerns about antibiotic resistance and lacks generalizability. Participants indicated equipoise with regard to benefits and harms of SDD, and indicated strong support for a further randomised trial.

Conclusions

Clinicians have clinical equipoise about the effectiveness of SDD. Future research requires longer follow up to assess antibiotic resistance as well as greater validity/generalizability to provide definitive answers on the effectiveness of decontamination and effects on antibiotic resistance. SDD was regarded as not being a high clinical priority, which may limit future trial participation. These results have identified that further large randomised controlled trial of SDD in critical care is both warranted and appropriate.     

Targeting miR-21 for the Therapy of Pancreatic Cancer

Despite tremendous efforts worldwide from clinicians and cancer scientists, pancreatic ductal adenocarcinoma (PDA) remains a deadly disease for which no cure is available. Recently, microRNAs (miRNAs) have emerged as key actors in carcinogenesis and we demonstrated that microRNA-21 (miR-21), oncomiR is expressed early during PDA. In the present study, we asked whether targeting miR-21 in human PDA-derived cell lines using lentiviral vectors (LVs) may impede tumor growth. We demonstrated that LVs-transduced human PDA efficiently downregulated miR-21 expression, both in vitro and in vivo. Consequently, cell proliferation was strongly inhibited and PDA-derived cell lines died by apoptosis through the mitochondrial pathway. In vivo, miR-21 depletion stopped the progression of a very aggressive model of PDA, to induce cell death by apoptosis; furthermore, combining miR-21 targeting and chemotherapeutic treatment provoked tumor regression. We demonstrate herein for the first time that targeting oncogenic miRNA strongly inhibit pancreatic cancer tumor growth both in vitro and in vivo. Because miR-21 is overexpressed in most human tumors; therapeutic delivery of miR-21 antagonists may still be beneficial for a large number of cancers for which no cure is available.     

The Practitioner Proposes a Treatment Change and the Patient Declines: What to do next?

Abstract Objective: This study describes how pain practitioners can elicit the beliefs that are responsible for patients’ judgments against considering a treatment change and activate collaborative decision making. Methods: Beliefs of 139 chronic pain patients who are in treatment but continue to experience significant pain were reduced to 7 items about the significance of pain on the patient’s life. The items were aggregated into 4 decision models that predict which patients are actually considering a change in their current treatment. Results: While only 34% of study participants were considering a treatment change overall, the percentage ranged from 20 to 70, depending on their ratings about current consequences of pain, emotional influence, and long‐term impact. Generalized linear model analysis confirmed that a simple additive model of these 3 beliefs is the best predictor. Conclusion: Initial opposition to a treatment change is a conditional judgment and subject to change as specific beliefs become incompatible with patients’ current conditions. These beliefs can be elicited through dialog by asking 3 questions.     

Amphetamine actions at the serotonin transporter rely on the availability of phosphatidylinositol-4,5-bisphosphate

Nerve functions require phosphatidylinositol-4,5-bisphosphate (PIP₂) that binds to ion channels, thereby controlling their gating. Channel properties are also attributed to serotonin transporters (SERTs); however, SERT regulation by PIP₂ has not been reported. SERTs control neurotransmission by removing serotonin from the extracellular space. An increase in extracellular serotonin results from transporter-mediated efflux triggered by amphetamine-like psychostimulants. Herein, we altered the abundance of PIP₂ by activating phospholipase-C (PLC), using a scavenging peptide, and inhibiting PIP₂-synthesis. We tested the effects of the verified scarcity of PIP₂ on amphetamine-triggered SERT functions in human cells. We observed an interaction between SERT and PIP₂ in pull-down assays. On decreased PIP₂ availability, amphetamine-evoked currents were markedly reduced compared with controls, as was amphetamine-induced efflux. Signaling downstream of PLC was excluded as a cause for these effects. A reduction of substrate efflux due to PLC activation was also found with recombinant noradrenaline transporters and in rat hippocampal slices. Transmitter uptake was not affected by PIP₂ reduction. Moreover, SERT was revealed to have a positively charged binding site for PIP₂. Mutation of the latter resulted in a loss of amphetamine-induced SERT-mediated efflux and currents, as well as a lack of PIP₂-dependent effects. Substrate uptake and surface expression were comparable between mutant and WT SERTs. These findings demonstrate that PIP₂ binding to monoamine transporters is a prerequisite for amphetamine actions without being a requirement for neurotransmitter uptake. These results open the way to target amphetamine-induced SERT-dependent actions independently of normal SERT function and thus to treat psychostimulant addiction.