Association of dynamics of anellovirus loads with hospital-acquired pneumonia in brain-injured patients during the intensive care unit stay.

BACKGROUND: Critical illness induces immune disorders associated with an increased risk of hospital-acquired pneumonia (HAP) and acute respiratory distress syndrome (ARDS). Torque Teno Virus (TTV), from the Anelloviridae family, are proposed as a biomarker to measure the level of immunosuppression. Our objective was to describe the kinetics of TTV DNA loads and their association with critical-illness related complications. METHODS: We performed a longitudinal study in 115 brain-injured patients from a prospective cohort, collected endotracheal and blood samples at three time points (T1, T2, T3) during the two weeks post-admission in intensive care unit, and measured viral DNA loads using the TTV R-gene® kit (Biomerieux) and a pan-Anelloviridae in house qRT-PCR. RESULTS: TTV DNA was detected in the blood of 69, 71, and 64% of brain-injured patients at T1, T2 and T3 respectively. Time-associated variations of TTV and Anellovirus (AV) DNA loads were observed. Using a linear mixed-effects model, we found that HAP and ARDS were associated with lower blood AV DNA loads. CONCLUSION: Our results show that HAP or ARDS in critically ill patients are associated to changes in AV DNA loads, and should be evaluated further as a biomarker of immune disorders leading to these complications.

Evolution of sexual functioning of men through treated and untreated depression.

OBJECTIVES: Depression as well as a treatment by antidepressant are factors that may interfere with sexuality. Due to this complex relationship between depression, antidepressant and sexuality, it is difficult to incontestably establish the exclusive accountability of a treatment or of a psychiatric disorder on sexual dysfunctions. The main purpose of the SADD (for Sexuality, Anti-Depressant and Depression) study is to evaluate sexual dysfunctions in depressed men treated with antidepressant or not. METHODS: Participants of this transversal, observational study were men aged over 18 years old, suffering from unipolar major depressive disorder and treated by a psychiatrist, with or without antidepressant. Assessment of sexual functioning through three times: euthymia (before depression), untreated depression and treated depression if applicable was performed based on the ASEX scale. RESULTS: Seventy patients were included. Eight percent of euthymic patients presented a sexual dysfunction (average score on the ASEX=12.4) whereas 56% of untreated patients presented a sexual dysfunction (average total score on the ASEX=17.7) and 62% (34/55) of patients treated with antidepressant (average total score on ASEX=18.5) (P<0.001). Sexual functioning of men receiving treatment is not significantly different to that among men not receiving any antidepressant, even if patients treated with antidepressant reported that they had a better mood than those untreated. CONCLUSIONS: Our results reveal a high prevalence of sexual dysfunction within the framework of major depressive disorder and its treatment and underlines the complex relationship between major depressive disorder, antidepressant and sexuality.

[Treatments for depression in consultation-liaison psychiatry: From theory to practice]. / Les traitements de la dépression en psychiatrie de liaison : de la théorie à la pratique.

Treatments for depression include an adapted lifestyle, physical activity, psychotherapies, antidepressant and mood stabilizing drugs, neuromodulation, chronotherapy, spa treatments. Drug treatments used for major depressive episode are antidepressants and mood stabilizers. For a mild episode, psychotherapy is indicated. It should be combined with an antidepressant (serotonin reuptake inhibitor) for moderate and severe episodes. Suicide risk assessment is essential throughout the depressive episode. It is recommended to monitor at the start of antidepressant treatment for suicidal behavior, a change in mood suggesting an underlying bipolar disorder. The effectiveness of the treatment is evaluated after 4 to 8 weeks. The total duration of antidepressant treatment for an EDC is between 6 months and 1 year after remission, in order to prevent relapses. The use of liaison psychiatry, a real healthcare system within the general hospital, is strongly recommended for better screening and treatment of depression, thus reducing the length of hospital stays, improving the prognosis of depression. The aim of this article is to provide clinicians with a summary of validated data on the efficacy/tolerance of treatment for depression, and to suggest practical action to be taken on the main daily clinical situations: treating comorbid conditions, taking into account interactions drugs, manage the serotonin syndrome, lead to withdrawal from antidepressants, manage treatment in the elderly.

[Recommendations for a gradual and controlled resumption of electroconvulsive therapy in France during the period of lifting of the containment and of the COVID-19 pandemic linked to SARS-CoV-2]. / Recommandations pour une reprise progressive et contrôlée de l'électroconvulsivothérapie en France en période de levée du confinement et de pandémie COVID-19 liée au SARS-CoV-2.

The COVID-19 pandemic has had major consequences for the organization of care. In France and around the world, centers practicing electroconvulsive therapy (ECT) have seen their activity decrease, or even stop for many reasons. In this context, maintaining or resuming this essential therapeutic activity for many patients suffering from psychiatric disorders requires material, human and logistical adaptations that should be supervised. The objective of this collective and national work is to offer simple recommendations that can be applied immediately by any healthcare establishment, public or private, practicing ECT. They are the result of feedback from multiprofessional and inter-establishment experiences. Declined in three stages, these recommendations are accompanied by a practical sheet which describes in detail the necessary conditions and prerequisites for any resumption of ECT activity.

[Evolution of electro-convulsive therapy activity in France since the beginning of the COVID-19 pandemic]. / Évolution de l'activité d'électro-convulsivo-thérapie en France depuis le début de la pandémie COVID-19.

The recent COVID-19 pandemic has led to major organisational changes in health care settings, especially in psychiatric hospitals. We conducted a national online survey to assess the evolution of electroconvulsive therapy (ECT) in the different centres practicing this treatment. 65 responses from all over France were analysed. More than 90 % of the centres practising ECT experienced a decrease in their activity. Half of the centres experienced a total cessation of activity and 25 % of the centres experienced a decrease of more than half of their usual activity. Post-pandemic COVID-19 psychiatric care is expected to be difficult. It is essential not to add to this difficulty the complications, often serious, that will be associated with delaying or stopping the practice of ECT. It will also be necessary to remain vigilant with regard to the specific neuropsychiatric consequences that will follow the pandemic.

[Health professionals facing the coronavirus disease 2019 (COVID-19) pandemic: What are the mental health risks?] / Les professionnels de santé face à la pandémie de la maladie à coronavirus (COVID-19) : quels risques pour leur santé mentale ?

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic. METHODS: Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms. RESULTS: The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications. CONCLUSIONS: In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.

Adherence to treatment guidelines in clinical practice for using electroconvulsive therapy in major depressive episode.

BACKGROUND: ECT is the most effective treatment of major depressive episode (MDE) but remains a neglected treatment. The French Society for Biological Psychiatry and Neuropsychopharmacology aimed to determine whether prescribing practice of ECT followed guidelines recommendations. METHODS: This multicenter, retrospective study included adult patients with major depressive disorder (MDD) or bipolar disorder (BD), who have been treated with ECT for MDE. Duration of MDE and number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: Seven hundred and forty-five individuals were included. The mean duration of MDE before ECT was 10.1 months and the mean number of lines of treatment before ECT was 3.4. It was significantly longer for MDD single episode than recurrent MDD and BD. The presence of first-line indications for using ECT was significantly associated to shorter duration of MDE (9.1 vs 13.1 months, p<0.001) and lower number of lines of treatment before ECT (3.3 vs 4.1, p<0.001). LIMITATIONS: This is a retrospective study and not all facilities practicing ECT participated that could limit the extrapolation of the results. CONCLUSION: Compared to guidelines, ECT was not used as first-line strategy in clinical practice. The presence of first-line indications seemed to reduce the delay before ECT initiation. The improvements of knowledge and access of ECT are needed to decrease the gap between guidelines and clinical practice.

Psychiatric disorders, acne and systemic retinoids: comparison of risks.

BACKGROUND: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids. MATERIALS AND METHODS: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest. RESULTS: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin. CONCLUSION: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.

Benzodiazepine dependence in subjects with alcohol use disorders: what prevalence?

OBJECTIVE: To our knowledge, no studies have been conducted in France on benzodiazepine (BZD) dependence among outpatients with alcohol use disorders (AUD). Some international studies have been conducted on the consumption of BZD in this specific population, but the comparisons among them are difficult. We aimed to assess the current prevalence of probable benzodiazepine and BZD-like hypnotics (Z-drugs) dependence among outpatients seeking treatment for AUD. METHODS: Participants were patients seeking treatment for AUD for the first time or repeating treatment after more than twelve months. Recruitment took place in seven addiction centres between January and December 2013 in the Nantes region (France). BZD/Z-drug dependence was assessed according to the DSM-IV diagnostic criteria for dependence. This information was gathered through a self-report questionnaire. RESULTS: Among the 1005 patients included in this study, 413 were BZD/Z-drug users (41.1%). Among the 413 patients, 217 were probably dependent on at least one substance, which represents 21.6% of the total population and 52.5% of BZD/Z-drug users. CONCLUSION: BZD/Z-drug dependence represents a public health concern. Prescribers should take the risks into account and keep treatment courses to a minimum.

[Hospital production cost of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression]. / Coût de production hospitalier de la stimulation magnétique transcrânienne répétée (rTMS) dans le traitement de la dépression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective and well-tolerated treatment in resistant depression with mild to moderate intensity. This indication has not yet been approved in France. The cost and medico-economic value of rTMS in psychiatry remains unknown. The aim of this preliminary study was to assess rTMS cost production analysis as an in-hospital treatment for depression. METHODS: The methodology, derived from analytical accounts, was validated by a multidisciplinary task force (clinicians, public health doctors, pharmacists, administrative officials and health economist). It was pragmatic, based on official and institutional documentary sources and from field practice. It included equipment, staff, and structure costs, to get an estimate as close to reality as possible. First, we estimated the production cost of rTMS session, based on our annual activity. We then estimated the cost of a cure, which includes 15 sessions. A sensitivity analysis was also performed. RESULTS: The hospital production cost of a cure for treating depression was estimated at € 1932.94 (€ 503.55 for equipment, € 1082.75 for the staff, and € 346.65 for structural expenses). CONCLUSION: This cost-estimate has resulted from an innovative, pragmatic, and cooperative approach. It is slightly higher but more comprehensive than the costs estimated by the few international studies. However, it is limited due to structure-specific problems and activity. This work could be repeated in other circumstances in order to obtain a more general estimate, potentially helpful for determining an official price for the French health care system. Moreover, budgetary constraints and public health choices should be taken into consideration.

Promoter element spacing controls basal expression and light inducibility of the cyanobacterial secA gene.

The Synechocystis PCC6803 secA gene was found to be essential for cell viability and to be transcriptionally controlled by the redox state of the cells. The basic promoter (BP, -71 to +47 relative to the transcription start site) is controlled by three cis-acting elements, which together mediate the fourfold light induction of BP activity. The positively acting element (PE1, -361 to -71) upstream of BP exerts a twofold stimulation of BP; the negative element (NE, +47 to +104) downstream of BP decreases BP strength about sixfold. The PE2 element (+104 to +175) lying in the coding sequence overcomes NE-dependent downregulation of BP. BP harbours Escherichia coli sigma70-like promoter elements -35 (5'-TTGAat-3') and -10 (5'-TAagAT-3'). The -10 motif, which has the features of an 'extended -10' box, is absolutely essential to promoter activity. The -35 hexamer is critical to the enhancement of promoter strength above BP level and to light inducibility, both features involving regulatory elements flanking BP. Most interestingly, reducing the length of the 30 bp spacing between the -35 and -10 boxes down to 17 bp was found to increase promoter activity and to confer light inducibility to BP. This demonstrates that promoter element spacing controls basal expression and light inducibility of the secA gene.

Light-regulated promoters from Synechocystis PCC6803 share a consensus motif involved in photoregulation.

A library of Synechocystis PCC6803 (S.6803) DNA cloned in front of the promoterless cat reporter gene of the plasmid pFF11 was used to transform S.6803 to high light-dependent resistance to chloramphenicol. In five clones harbouring a stably replicating pFF11-derived plasmid, this phenotype occurred independently of the photosystem II electron transport and resulted from the correlated increase of CAT activity level and cat mRNA accumulation. The five promoter inserts contained no Escherichia coli sigma 70 promoter element, in agreement with their lack of activity in this organism, but shared two conserved motifs. Two secondary mutations, which restored light-regulated promoter activity to an inactive mutant of the smallest insert, mapped within one of the common motifs, emphasizing the probable involvement of this element in photoregulation.

A conjugative plasmid vector for promoter analysis in several cyanobacteria of the genera Synechococcus and Synechocystis.

A promoter-probe vector, pSB2A, based on the plasmid RSF1010 and the promoterless chloramphenicol acetyl transferase (cat) reporter gene, has been constructed. pSB2A appeared to be most efficiently transferred by conjugation to the widely used cyanobacteria Synechocystis strains PCC6803 (S.6803) and PCC6714 (S.6714) and Synechococcus strains PCC7942 (S.7942) and PCC6301 (S.6301), where it replicates stably even though it contains no cyanobacterial DNA. Using pSB2A we found that (1) a light-regulated promoter from S.6803 remains controlled by light intensity in S.7942 while it is silent in Escherichia coli, and (2) the E. coli tac promoter behaves as a strong and light-independent promoter in the four cyanobacterial hosts tested.