Effect of intravenous ferric carboxymaltose supplementation in non-anaemic iron deficient patients undergoing hip and knee arthroplasty.

Preoperative anaemia and non-anaemic iron deficiency are independent risk factors for perioperative blood transfusion, morbidity, and mortality. Although the efficacy to treat anaemia with iron infusion before elective surgery has been widely studied, the literature offers few data about the efficacy of treating iron deficient, non-anaemic patients before elective surgery. This retrospective study assessed the effect of preoperative ferric carboxymaltose (FC) administration on the concentration of Haemoglobin (Hb) in iron deficient, non-anaemic individuals following total knee or hip arthroplasty. A treatment group of 83 non-anaemic iron deficient individuals scheduled for arthroplasty were administered a 1000mg FC infusion over 15 minutes 4 weeks prior to surgery. In the control group (n=62) FC was not administered preoperatively. No individual from either group was given any iron supplement following the pre-operative visit. Blood tests were performed and analysed 4-weeks before surgery, on admission, and then 2-days, 4-days and 4-weeks postoperatively. Number of blood transfusions performed and adverse events were recorded. Hb concentration did not change substantially after iron supplementation prior to surgery. No difference in the number of blood transfusions was observed. In the treatment, group postoperative Hb concentration recovered significantly more quickly compared to control (p=0.0047). No adverse event was reported. The administration of FC in non-anaemic iron deficient individuals quickens the restoration of Hb concentration following THA or TKA procedures.

[Suicidal risk prevention in schizophrenia: Importance of family psychoeducation]. / Prévention du risque suicidaire dans la schizophrénie : importance de la psychoéducation des familles.

OBJECTIVES: Although mortality by suicide in schizophrenia seems to have decreased in some countries over the last 30 years, it remains much higher than in the general population. Studies have shown this risk to impact around 5% of patients, corresponding to a risk almost 2.5 times higher than in the general population. Family psychoeducation in schizophrenia has been demonstrated to lead to symptom reductions and to an improvement of the quality of life, two factors that should contribute to decreasing the suicidal risk. Therefore, if families attend an efficient psychoeducation program, we can expect a decrease in the patient suicidal risk. Attending a family psychoeducation program at the beginning of the disease would also be associated with a stronger preventive effect on suicidal mortality. The objective of this study is to describe the suicide attempt rate of patients who suffer from schizophrenia before and one year after one of their relatives participated to the family psychoeducation program Profamille. METHOD: We performed a retrospective study on 1209 people who attended the Profamille (V3.2 version) Family Psychoeducation Program. This program has 2 modules: an initial training module of 14 weekly or fortnightly sessions, and a consolidation module of 4 sessions over 2 years. Sessions last 4 hours and follow a precise and structured course. Data were collected from 40 different centers in France, Belgium and Switzerland and were based on participants assessed at the beginning and one year after the first module. Self-assessment from the relatives participating in the program provided the measure of patients' suicide attempts. An assessment at T0 explored the attempts over the 12 months before the beginning of the program while the assessment at T1 analyzed those during the 12 months following the end of the Program. The Chi2 test was used to compare the suicide attempt rates for each period, using a significance threshold of 0.05. Since the risk of suicide is greater in the first years of the illness, rates of attempts are also calculated according to the age of disorder. The analysis was carried out with the statistical software R. RESULTS: The number of participants reporting that their relative had attempted suicide in the previous 12 months decreased from 41 to 21. The annual attempts rate was evaluated at 6.4 % before the Profamille program and decreased to 2.4 % a year after the end of the program (P=0.0003). The reduction of the attempt rate was observed even for patients with schizophrenia for more than 10 years. CONCLUSION: This study shows the positive impact of Profamille on reducing the rate of suicide attempts in patients with schizophrenia. It has been shown that the risk is highest at the beginning of the disorder. Therefore, based on our results, it would seem appropriate to propose the Profamille program at an early stage.

Tobacco smoking is associated with antipsychotic medication, physical aggressiveness, and alcohol use disorder in schizophrenia: results from the FACE-SZ national cohort.

Tobacco smoking is common in schizophrenia and is one of the main causes of premature mortality in this disorder. Little is known about clinical correlates and treatments associated with tobacco smoking in patients with schizophrenia. Still, a better characterization of these patients is necessary, in a personalized care approach. Aggressiveness and childhood trauma have been associated with tobacco smoking in general population, but this association has never been explored in schizophrenia. Our study examines the clinical and therapeutic characteristics of tobacco smoking in schizophrenia. 474 stabilized patients (mean age = 32.2; 75.7% male gender; smokers n = 207, 54.6%) were consecutively included in the network of the FondaMental Expert centers for Schizophrenia and assessed with valid scales. Current tobacco status was self-declared. Aggressiveness was self-reported with Buss-Perry Aggressiveness Questionnaire and Childhood Trauma with Childhood Trauma Questionnaire. Ongoing treatment was reported. In univariate analysis, tobacco smoking was associated with lower education level (p < 0.01), positive syndrome (p < 0.01), higher physical aggressiveness (p < 0.001), alcohol dependence (p < 0.001), and First Generation Antipsychotics (FGAs) use (p = 0.018). In a multivariate model, tobacco smoking remained associated with physical aggressiveness (p < 0.05), current alcohol dependence (p < 0.01) and FGA use (p < 0.05). No association was observed with childhood trauma history, mood disorder, suicidal behavior, psychotic symptom, global functioning or medication adherence. Patients with tobacco use present clinical and therapeutic specificities, questioning the neurobiological links between tobacco and schizophrenia. They could represent a specific phenotype, with specific clinical and therapeutic specificities that may involve interactions between cholinergic-nicotinic system and dopaminergic system. Further longitudinal studies are needed to confirm the potential efficacy of second generation antipsychotics (SGAs) on tobacco use in schizophrenia and to develop effective strategies for tobacco cessation in this population.

Chronic low-grade peripheral inflammation is associated with ultra resistant schizophrenia. Results from the FACE-SZ cohort.

A high rate of patients with schizophrenia (SZ) does not sufficiently respond to antipsychotic medication, which is associated with relapses and poor outcomes. Chronic peripheral inflammation has been repeatedly associated with schizophrenia risk and particularly to poor responders to treatment as usual with cognitive impairment in SZ subjects. The objective of present study was to confirm if ultra resistance to treatment in schizophrenia (UTRS) was associated to chronic peripheral inflammation in a non-selected sample of community-dwelling outpatients with schizophrenia. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. Current psychotic symptomatology was evaluated by the Positive and Negative Syndrome scale for Schizophrenia (PANSS). UTRS was defined by current clozapine treatment + PANSS total score ≥ 70. Functioning was evaluated by the Global Assessment of Functioning scale. High sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. 609 stabilized community-dwelling SZ subjects (mean age = 32.5 years, 73.6% male gender) have been included. 60 (9.9%) patients were classified in the UTRS group. In multivariate analyses, UTRS has been associated independently with chronic peripheral inflammation (OR = 2.6 [1.2-5.7], p = 0.01), illness duration (0R = 1.1 [1.0-1.2], p = 0.02) and impaired functioning (OR = 0.9 [0.9-0.9], p = 0.0002) after adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption. Peripheral low-grade inflammation is associated with UTRS. Future studies should explore if anti-inflammatory strategies are effective in UTRS with chronic low-grade peripheral inflammation.

Towards an improved access to psychiatric rehabilitation: availability and effectiveness at 1-year follow-up of psychoeducation, cognitive remediation therapy, cognitive behaviour therapy and social skills training in the FondaMental Advanced Centers of Expertise-Schizophrenia (FACE-SZ) national cohort.

Psychosocial Interventions (PIs) have shown positive effects on clinical and functional outcomes of schizophrenia (SZ) in randomized controlled trials. However their effectiveness and accessibility remain unclear to date in "real world" schizophrenia. The objectives of the present study were (i) to assess the proportion of SZ outpatients who benefited from PIs between 2010 and 2015 in France after an Expert Center Intervention in a national multicentric non-selected community-dwelling sample; (ii) to assess PIs' effectiveness at 1-year follow-up. 183 SZ outpatients were recruited from FondaMental Advanced Centers of Expertise for Schizophrenia cohort. Baseline and 1-year evaluations included sociodemographic data, current treatments, illness characteristics and standardized scales for clinical severity, adherence to treatment, quality of life, a large cognitive battery, and daily functioning assessment. Only 7 (3.8%) received a PI before the evaluation, and 64 (35%) have received at least one PI during the 1-year follow-up. Having had at least one PI during the follow-up has been associated in multivariate analyses with significantly higher improvement in positive and negative symptoms (respectively p =0.031; p = 0.011), mental flexibility (TMT B, p = 0.029; C-VF, p = 0.02) and global functioning (p =0.042). CBT and SST were associated with higher cognitive improvements, while CRT was associated with clinical improvement. These results have not been demonstrated before and suggest that the effect of each PI is larger than its initial target. The present study has confirmed the PIs' effectiveness in a large sample of community-dwelling SZ outpatients at 1 year follow-up. Efforts to improve access to PI should be reinforced in public health policies.

[The 10-year findings from the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ): Review and recommendations for clinical practice]. / Centres Experts Schizophrénie, un outil pour le soin et la recherche : retour sur 10 ans d'expérience.

OBJECTIVES: The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort. METHODS: More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers. RESULTS: The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset<19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy. CONCLUSIONS: In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.

Relationships between low-grade peripheral inflammation and psychotropic drugs in schizophrenia: results from the national FACE-SZ cohort.

Low-grade inflammation has repeatedly been associated with schizophrenia (SZ) and in particular with cognitive impairment. Female gender, overweight and tobacco smoking have been suggested as risk factors to increase inflammation while preclinical inconsistent findings have been found regarding the association with psychotropic drugs. The aim of this study was to explore if psychotropic drugs were associated with inflammation in SZ and to determine which psychotropic drug was associated with inflammation in stable SZ subjects while considering clinical confounding factors. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. High-sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. The zero-inflated Poisson regression model estimated the relationship between low-grade inflammation and psychotropic drug. Four hundred and five stabilized, community-dwelling SZ subjects (mean age = 32.6 years, 74% male gender) have been included. In total, 148 participants (36.5%) were found with undetectable blood hs-CRP level. The probability of having an undetectable CRP was associated with a lower body mass index (p < 0.0001) and no cyamemazine add-on antipsychotic therapy (p = 0.001). The other 257 participants (63.5%) were found to have low-grade inflammation (hs-CRP > 0 mg/L). Low-grade inflammation was significantly associated with female gender (p = 0.004), higher body mass index (p < 0.0001), current tobacco smoking (p < 0.0001), clomipramine (p = 0.04), quetiapine (p < 0.0001) and hypnotic (p = 0.0006) consumption while decreased hs-CRP blood levels was associated with aripiprazole (p = 0.004) and valproate/valpromide (p = 0.03) consumption. The present study suggests that some psychotropic drugs (quetiapine, cyamemazine, clomipramine) may be associated with increased peripheral low-grade inflammation in SZ patients while others (aripiprazole, valproate) may be associated with decreased peripheral low-grade inflammation. These results should be replicated in SZ and non-SZ populations and the biological underpinnings should be further explored.

Chronic low-grade peripheral inflammation is associated with severe nicotine dependence in schizophrenia: results from the national multicentric FACE-SZ cohort.

Chronic peripheral inflammation (CPI) has been associated with cognitive impairment in schizophrenia (SZ). However, its sources remain unclear, more specifically it is not known whether tobacco smoking is a source of inflammation or not in SZ subjects. Moreover, nicotine (NIC), the major psychoactive compound of tobacco, shows strong anti-inflammatory properties in vitro, as well as inducing a severe biological dependence when administered repeatedly. The objective of the present study was to determine if CPI was associated with tobacco smoking and/or NIC dependence in schizophrenia. Three hundred and forty five stabilized community-dwelling SZ subjects aged 16 years or older (mean age = 32 years, 73% male) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. CPI was defined by a highly sensitive C-reactive protein (hsCRP) ≥3 mg/L. Current tobacco status was self-declared. Severe NIC dependence was defined by a Fagerstrom Test for Nicotine Dependence score ≥7. Overall, 159 (46.1%) were non-smokers, 117 (33.9%) and 69 (20%) were current tobacco smokers with, respectively, low and severe nicotine dependence. In a multivariate model, CPI remained associated with severe NIC dependence (29 vs 15%, OR = 2.8, p = 0.003) and body mass index (OR = 1.1, p < 0.0001), independently of socio-demographic characteristics and antidepressant intake. No association of CPI with low to moderate tobacco smoking dependence, number of daily smoked cigarettes, cannabis use, alcohol use or illness characteristics was found (all p > 0.05). CPI was associated with severe NIC dependence but not with tobacco smoking with low to moderate NIC dependence in SZ, independently of socio-demographic variables, body mass index, alcohol consumption and antidepressant intake. This result highlights the potential CPI consequences of the high prevalence of heavy tobacco smoking in SZ, indicating the importance of new therapeutic strategies for tobacco cessation in SZ.

[French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression]. / Prise en charge des troubles dépressifs résistants : recommandations françaises formalisées par des experts de l'AFPBN et de la fondation FondaMental.

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

[Neurocognitive and psychiatric management of the 22q11.2 deletion syndrome]. / Perspectives actuelles dans la microdélétion 22q11.2 : prise en charge du phénotype neurocomportemental.

INTRODUCTION: The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22. 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). The inheritance of the syndrome (10%) is autosomal dominant. Most people with 22q11.2DS are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. A small percentage of affected individuals have shorter deletions in the same region (contiguous gene deletion syndrome). The general features of 22q11.2DS vary widely (more than 180 phenotypic presentations) and the syndrome is under diagnosed. Characteristic symptoms may include congenital heart disease, defects in the palate, neuromuscular problems, velo-pharyngeal insufficiency, hypoparathyroidism, craniofacial features and problems with the immune system T-cell mediated response (caused by hypoplasia of the thymus). COGNITIVE PHENOTYPE: The neurocognitive phenotype of the 22q11.2DS is complex. Cognitive deficits are seen in the majority (80-100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory and visual-spatial perception. Borderline intellectual function (IQ: 70-75) is most common, mild intellectual disability (IQ: 55-75) is slightly less frequent and a small percentage of children fall into the low average intelligence range. Most children with 22q11.2DS achieve higher scores in verbal tasks than in non-verbal tasks, although this pattern of dysfunction being not universal. Brain MRI studies have shown volumetric changes in multiple cortical and subcortical regions in individuals with 22q11DS that could be related to both cognition and psychoses. PSYCHIATRIC PHENOTYPE: General psychiatric features included anxiety disorders, attention deficit disorder and poor social skills (40-50%). An elevated risk of bipolar disorder and major depression occurs in adolescence and young adulthood. A strong and specific relationship exists between the presence of the 22q11.2 microdeletion and schizophrenia (30-40%). This risk is not associated with any other neurogenetic syndrome. Social cognition is impaired in 22q11.2 DS and this observation is correlated with psychotic features. So, long-term medical care is increasingly being directed towards the treatment and recognition of these symptoms. TREATMENT: Required pharmacological treatment strategies have to be adapted to the syndrome. Moreover, cognitive remediation is a promising tool for treating neuro- and social cognitive deficits in 22q11.2DS. However, these new therapeutic strategies have to be developed to improve quality of life.

Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: Results from the FACE-BD cohort.

Bipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted BD. Moreover, the validity of only one anticholinergic burden scale designed to assess the anticholinergic load of medications has been tested in BD. In a literature review, we identified 31 existing scales. We first measured the associations between 27 out of the 31 scales and objective cognitive impairment in bivariable regressions. We then adjusted the bivariable models with covariates: the scales significantly associated with cognitive impairment in bivariable and multiple logistic regressions were defined as having good concurrent validity to assess cognitive impairment. In a sample of 2,031 individuals with euthymic BD evaluated with a neuropsychological battery, two scales had good concurrent validity to assess cognitive impairment, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments had not. Finally, similar analyses with subjective anticholinergic side-effects as outcome variables reported 14 scales with good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 to assess self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in estimating iatrogenic cognitive impairment in studies investigating cognition in BD.

Clinical efficacy of implementing a Patient Blood Management (PBM) Protocol in joint replacement surgery: a retrospective cohort study in a national referral center.

OBJECTIVE: The aging of population has dramatically broadened the total number of Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA) performed worldwide. To optimize the number of blood transfusions performed, a multimodal and multidisciplinary approach was introduced, called Patient Blood Management (PBM). The aim of the present retrospective study is to evaluate the feasibility and clinical outcomes of a PBM protocol applied in a national referral center for joint replacement surgery. PATIENTS AND METHODS: Clinical reports of 9,635 patients undergoing primary THA or TKA, from 2014 to 2019, were screened. The trends of hemoglobin value at admission and at day 4 after surgery were analyzed. Furthermore, the trend of blood bags' requests and blood transfusions was longitudinally evaluated to assess the efficacy of our PBM protocol and its potential impact in reducing the length of stay in the hospital. RESULTS: In 2014, mean hemoglobin (Hb) levels at postoperative day 4 were 10.3 g/dl and 10.2 g/dl for TKA (unilateral and bilateral, respectively), and in 2019 were 11.3 g/dl and 11.6 g/dl (unilateral and bilateral, respectively, p=0.001). Total requested red blood cell (RBC) transfusions by each surgery over time have decreased for THA (277 in 2014 vs. 120 in 2019, p=0.001).  A correlation matrix analysis between Hb level, body mass index (BMI), age, days spent in orthopedic (OR) ward and number of requested transfusions showed that RBC bags transfusions were related to the length of the hospital stay. CONCLUSIONS: A timely application of a PBM protocol in the perioperative period of TKA and THA was significantly associated to the reduction of blood transfusions and total length of hospital stay, with clear benefits for both the patients and the hospital.

A rapid recovery protocol for hip and knee replacement surgery: a report of the outcomes in a referral center.

OBJECTIVE: The number of joint replacements is expected to dramatically increase, and the optimization of the available resources is fundamental to maintain high clinical standards while providing an efficient treatment to an increasing number of patients. The present study describes the outcomes of the application of a rapid recovery (RR) protocol in a referral center for hip and knee replacement surgery. PATIENTS AND METHODS: The medical records of every patient undergoing primary hip or knee replacement in 2019 were identified and all the relevant data were retrospectively extracted and compared to those of year 2016 (the last year before the onset of the rapid recovery protocol). The following outcomes were considered: 1) length of stay (LOS); 2) total number of TKR and THR; 3) pre- and post-operative subjective questionnaires; 4) NRS for pain at day 1 following surgery; 5) mean hemoglobin value at discharge; 6) number of blood transfusion performed; 7) complications following surgery. RESULTS: The mean LOS was significantly lower for patients managed through the rapid recovery protocol: 5.1 ± 1.4 days vs. 10.4 ± 2.3 days (p < 0.0001). The earlier discharge of patients promoted an overall increase in the total number of joint replacement procedures performed (2,806 in year 2019 vs. 2,236 in year 2016; p < 0.0001). Higher hemoglobin values at discharge were found in the RR group (10.6 ± 1.4 g/dl vs. 9.6 ± 1.2 g/dl, p = 0.049). No difference was observed in terms of clinical scores and overall complication rate. CONCLUSIONS: The application of a multimodal RR protocol for THR and TKR patients was able to reduce the length of stay and optimize the use of blood products, without increasing the risk of complications or jeopardizing the functional recovery.

Recommendations of the schizophrenia expert center network for the screening prevention and treatment of sleep disorders based on the results from the real-world schizophrenia FACE-SZ national cohort.

BACKGROUND: Sleep disorders associated factors are under explored in schizophrenia while the literature suggests high and heterogeneous frequency. AIMS: The objective of the present study was to determine the prevalence and risk factors of sleep disorders in the real-world FACE-SZ national cohort. METHOD: Stabilized schizophrenic outpatients were recruited in 10 expert centers for schizophrenia. Sleep quality was explored with the Pittsburgh Sleep Quality Index (PSQI) and sleep disorders was defined by a PSQI score > 5. Psychosis severity was measured with the Positive and Negative Syndrome Scale, current major depressive episode with the Calgary Depression Scale for Schizophrenia, verbal aggressiveness with the Buss-Perry Aggression Questionnaire, adherence to treatment with the Medication Adherence Rating Scale, akathisia with the Barnes Akathisia Scale. Current somatic comorbidities and body mass index were reported. Variables with P values <0.20 in univariate analysis were included in a multivariate regression model. RESULTS: Of the 562 included patients, 327 subjects (58.2%, IC95% [54.1% - 62.3%]) reported having sleep disorders. After adjustment, sleep disorders were significantly associated with migraine (adjusted odds ratio aOR = 2.23, p = 0.041), major depressive disorder (aOR 1.79, p = 0.030), poor adherence to treatment (aOR = 0.87, p = 0.006), akathisia (aOR = 1.29, p = 0.042) and verbal aggressiveness (aOR = 1.09, p = 0.002). CONCLUSIONS: More than one on two stabilized real-life outpatients with schizophrenia have been identified with sleep disorders. Combined with the literature data, we have yielded expert recommendations for the treatment and prevention of sleep disorders including treating undiagnosed comorbid depression and migraine and managing antipsychotic treatment to improve adherence and akathisia.

Major depression, sleep, hostility and body mass index are associated with impaired quality of life in schizophrenia. Results from the FACE-SZ cohort.

BACKGROUND: Impaired Quality of life (QoL) in schizophrenia has been mostly associated with psychotic and mood symptomatology, insight and functioning so far. AIMS: QoL levels remain unsatisfactory due to other factors we aim to explore. METHOD: We have explored sleep quality with the Pittsburgh Sleep Quality Index, hostility with the Buss&Perry questionnaire, major depression with the Positive and Negative Syndrome Scale depressive factor, functioning with the Global Assessment of Functioning scale and weight gain with body mass index in addition to other classical QoL-associated factors. RESULTS: 559 patients (mean age=31 (SD 9) years, 74% male sex) were included in the national FACE-SZ cohort. Impaired QoL has been significantly associated with respectively major depression, impaired sleep quality, increased hostility, impaired functioning and impaired insight independently of age, sex, treatments, tobacco smoking and body mass index. Major depression was associated with impaired psychological and physical well-being, and impaired self-esteem. Impaired sleep quality has been associated with impaired psychological and physical well-being and sentimental life. Hostility has been associated with impaired psychological well-being and self-esteem, impaired friends' relationships and impaired autonomy. Weight was associated with impaired physical well-being. Tobacco smoking was associated with higher level of friends' relationships. CONCLUSIONS: Major depression, sleep, hostility, and weight gain have been identified as potential targets to improve QoL in schizophrenia and should be implemented in the recommendations for good practice to optimize schizophrenia care.

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.

Confirmations, advances and recommendations for the daily care of schizophrenia based on the French national FACE-SZ cohort.

BACKGROUND: The National FondaMental Centers of Expertise (FACE) for Schizophrenia (SZ) have been created to shorten the gap between research and clinical practice. OBJECTIVES: To synthetize in a review the 10-year findings issued from the FACE-SZ cohort analyses. METHODS: More than 1000 patients were evaluated in 10 expert centers since 2010 with a 2-day long comprehensive standardized battery including neuropsychological testes and physical health assessment and followed-up for 3 years. RESULTS: 1. The phase 0 cross-sectional analyses have confirmed well-known data: over-prescription of first-generation antipsychotics, antipsychotic polytherapy and long-term benzodiazepine and under-prescription of clozapine, 13% of drug-induced parkinsonism, 18% of akathisia, a mean duration of untreated psychosis of 18 months, one third of poorly-adherent patients, 24% of metabolic syndrome and 52% of current tobacco smokers with poor care for physical illnesses; a yearly mean financial cost of 15,000 euro/patient. 2. FACE-SZ also yielded additional data in insufficiently explored area: a half of major depression issues (among them one third of undiagnosed major depression and 44% of treated patients with unremitted depression), major depression having a strong impact on Quality of Life independently of negative symptoms, 22% of moderated to severe untreated physical pain. 3. FACE-SZ has explored emerging fields of research, including development of 4 stages- model of schizophrenia, chronic low-grade peripheral inflammation, latent Toxoplasma infection, hypovitaminosis D, and a model for relapse prediction at 2 years. DISCUSSION: The associated factors and implications for public health programs were discussed. Based on the FACE-SZ findings and literature, the FACE-SZ group has yielded recommendations to improve daily care for schizophrenia and for future research.

[The serotonin syndrome: An updated literature review]. / Le syndrome sérotoninergique : une revue actualisée de la littérature.

The serotonin syndrome is a potentially deadly complication resulting from drug adverse effect, drug-drug interaction or overdose involving one or more serotonergic molecules, e.g., antidepressants, psychostimulants and sometimes an "ignored" serotonergic compound. The serotonin syndrome typically consists of a clinical triad including cognitive/behavioral, neurovegetative and neuromuscular features. However, this syndrome is characterized by major clinical heterogeneity, making the diagnosis difficult in practice. Moreover, many practitioners are quite unaware of this syndrome. Available scores and classifications can help physicians in their diagnosis approach. Knowing the responsible molecules, their potential interactions and mechanisms of action can help preventing this complication allowing therapeutic education among patients. This updated article reviews the clinical presentation, prevention, management, and pathophysiology of the serotonin syndrome, and addresses the most recent advances in pharmacogenetics regarding this syndrome.

A multi-dimensional approach to the relationship between insight and aggressiveness in schizophrenia: Findings from the FACE-SZ cohort.

BACKGROUND: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity. METHODS: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS). RESULTS: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger. CONCLUSION: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.

Inflammatory DEpression Advances in Schizophrenia (IDEAS): A precision medicine approach of the national FACE-SZ cohort.

BACKGROUND: Major Depressive Disorder (MDD) is a therapeutic challenge in schizophrenia (SZ). Untangling different forms of MDD appears as the best current strategy to improve remission to treatment in the so-called precision medicine approach. AIMS: The objectives of the present study were to determine (i) the prevalence of Inflammatory Depression (ID) in stabilized SZ outpatients (ii) if ID was associated with clinical or cognitive profiles that may help clinicians detecting ID (iii) if antidepressants were effective in ID and (iv) the biological correlates of ID that may orientate personalized treatments. METHOD: Participants were consecutively included and received a thorough 2 days- clinical assessment. RESULTS: 785 subjects were recruited in the FACE-SZ cohort. 289 (36.8%) were diagnosed with MDD (remitted or unremitted), of them 57 with ID (19.7%). No clinical or cognitive features were associated with ID (all p > 0.05). ID has been associated with increased abdominal perimeter (aOR = 4.48, p = 0.002) and latent Toxoplasma infection (aOR = 2.19, p = 0.04). While antidepressants were associated with decreased depressive symptoms level in ID, 44% of the subjects remained unremitted under antidepressant, with no association with CRP blood levels. CONCLUSIONS: ID may not differ from other forms of depression by its clinical symptoms but by its aetiologies. ID is associated with increased perivisceral fat and latent Toxoplasma infection that are both potentially related to gut/microbiota disturbances. Specific anti-inflammatory drugs and microbiota-targeted therapeutics appear as promising strategies in the treatment of inflammatory depression in schizophrenia.