Efficacy of shared decision-making on treatment adherence of patients with bipolar disorder: a cluster randomized trial (ShareD-BD).

BACKGROUND: Shared decision-making (SDM) is a model of interaction between doctors and patients in which both actors contribute to the medical decision-making process. SDM has raised great interest in mental healthcare over the last decade, as it is considered a fundamental part of patient-centered care. However, there is no research evaluating the efficacy of SDM compared to usual care (CAU), as it relates to quality of care and more specifically treatment adherence, in bipolar disorder (BD). METHODS/DESIGN: This is a 12-month multi-centre, cluster-randomized controlled trial comparing the efficacy of SDM to CAU. Adult BD patients (n = 300) will be eligible after stabilization for at least 4 weeks following an acute mood episode. The intervention will consist of applying the standardized SDM process as developed by the Ottawa Hospital Research Institute in order to choose the maintenance treatment of BD. A multidisciplinary team developed a decision aid "choose my long-term treatment with my doctor" for BD patients to clarify possible therapeutic options. Primary outcome will assess the patient's level of adherence (based on hetero-evaluation) of ongoing treatment at 12 months. Secondary outcomes will assess the difference between the 2 groups of patients in terms of adherence to maintenance drug therapy based on other measures (self-assessment scale and plasma levels of mood stabilizers). Additionally, other dimensions will be assessed: decisional conflict, satisfaction with care and involvement in decision making, beliefs about treatment, therapeutic relationship, knowledge about information for medical decision and clinical outcomes (depression, mania, functioning and quality of life). The primary endpoint will be analysed without adjustment by comparison of adherence scores between the two groups using Student t-tests or Mann-Whitney tests according to the variable distribution. A set of secondary analyses will be adjusted for covariates of clinical interest using generalized linear mixed regression models. DISCUSSION: This will be the first study evaluating the effect of an SDM intervention on patient adherence in BD. This is also an innovative protocol because it proposes the development of an evidence-based tool that should help patients and clinicians to initiate discussions regarding the use of BD treatment. TRIAL REGISTRATION: The study has been registered with ClinicalTrials.gov as NCT03245593 .

Identification of G2607A mutation in EGFR gene with a significative rate in Moroccan patients with Bladder Cancer.

The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of bladder cancer. A total, 50 Moroccan patient specimens with bladder cancer and 48 healthy controls were analysed for EGFR mutations in the region delimiting exons 18-21 by PCR amplification and direct sequencing. Our results showed the absence of mutations in the EGFR kinase domain in these exons in all analysed specimens. However, sequence analysis of the EGFR-TK domain, revealed the presence of (G2607A) polymorphism at exon 20. Statistical analysis showed significant difference in the frequencies of G2607A polymorphism between cancer cases and healthy controls (p=0.0001) and the frequencies of the GG and GA/AA genotypes among the cancer cases were 28% and 72%, respectively. Moreover, allelic frequencies of G2607A polymorphism showed significant difference between cancer cases and healthy controls (p=0.0025). Data analysis showed no significant association between G2607A polymorphism and patients' age, clinical stage and tumor grade (p > 0.05). However, a significant difference was found between this polymorphism and patients' sex that could be a sampling bias due to the very limited number of women with bladder cancer. Our findings highlight that, mutations in EGFR kinase domain is a rare event in bladder cancer, suggesting, that treatment of bladder cancer patients with TKI may not be effective. However, the EGFR G2607A polymorphism in exon 20 is frequent in bladder cancer cases and must be further explored for its relevance in the treatment of this disease.

[Association between the violence in the community and the aggressive behaviors of psychotics during their hospitalizations]. / Relation entre la violence intra-hospitalière des patients avec psychoses et la violence dans la communauté.

BACKGROUND: Violence is a common issue in psychiatry and has multiple determiners. The aim of this study is to assess the psychotic inpatients' violence in association with the violence of the neighborhood from which the patients are drawn and to estimate the impact of this environmental factor with regard to other factors. METHOD: A prospective multicenter study was led in nine French cities. Eligible patients were psychotic involuntary patients hospitalized in the cities' psychiatric wards. During their treatments, any kind of aggressive behavior by the patients has been reported by the Overt Aggression Scale (OAS). RESULTS: From June 2010 to May 2011, 95 patients have been included. Seventy-nine per cent of the patients were violent during their hospitalizations. In a bivariate analysis, inpatient violence was significantly associated with different factors: male gender, patient violence history, substance abuse, manic or mixed disorder, the symptoms severity measured by the BPRS, the insight degree and the city crime rate. In a multivariate analysis, the only significant factors associated with the patients' violence were substance abuse, the symptoms severity and the crime rates from the different patients' cities. CONCLUSION: These results suggest that violence within the psychotic patients' neighborhood could represent a risk of violence during their treatments.

Association between GPX1 Pro189Leu polymorphism and the occurrence of bladder cancer in Morocco.

Worldwide, Bladder cancer is the most frequent male malignancy. It is the third most common male malignancy in Morocco. The risk factors for developing bladder cancer are multiples including dietary conditions, environmental exposure and oxidative stress. GPX1 gene encoding for the human cellular antioxidant enzyme glutathione peroxidase1 is a key factor in the cell detoxification process. GPX1 Pro198Leu polymorphism is associated with a decrease of enzyme activity and may contribute to bladder cancer susceptibility. The present case-control study was planned to assess the presence of GPX1 Pro198Leu polymorphism in Moroccan population to determine whether it is associated with the risk of developing bladder cancer in Moroccan patients. A total of 32 patients with bladder cancer and 40 healthy controls were enrolled. Genotyping of the GPX1 Pro198Leu polymorphism was carried out by PCR amplification and DNA sequencing. Pro198Leu polymorphism was observed in both bladder cancer patients and healthy controls. No significant association between the polymorphism and bladder cancer occurrence was found (Pro/Leu vs. Pro/Pro: p=0.425; Leu vs. Pro: p=0.435). For the analysis of Pro198Leu polymorphism and progression of bladder cancer, no association was observed neither for stages (Pro/Leu vs. Pro/Pro: p=0.500; Leu vs. Pro: p=0.500) nor grades (Pro/Leu vs. Pro/Pro: p=0.415; Leu vs. Pro: p=0.427). Our results clearly showed no significant association between Pro198Leu polymorphism and risk of bladder cancer in our population, suggesting that the effect of this polymorphism on bladder cancer development might be a result of a combination with other genetic alterations and/or non-genetic variables such as diet and lifestyle factors.

[French Society for Biological Psychiatry and Neuropsychopharmacology task force. Formal consensus for the treatment of bipolar disorder: an update (2014)]. / Recommandations Formalisées d'Experts de l'Association Française de Psychiatrie Biologique et Neuropsychopharmacologie sur le dépistage et prise en charge du trouble bipolaire : mise à jour 2014.

As part of a process to improve the quality of care, the French Society for Biological Psychiatry and Neuropsychopharmacology developed in 2010 formal consensus guidelines for the treatment of bipolar disorder. The evolution of therapeutic options available in France for the treatment of bipolar disorder has justified the update of this guideline. The purpose of this work was to provide an updated and ergonomic document to promote its use by clinicians. This update focuses on two of the six thematic previously published (acute treatment and long-term treatment). Aspects of the treatment of bipolar patients sparking debate and questions of clinicians (use of antidepressant, place of the bitherapy, interest of long-acting antipsychotics…) were also covered. Finally, we proposed graded recommendations taking into account specifically the risk-benefit balance of each molecule.

[French Society for Biological Psychiatry and Neuropsychopharmacology task force: Formal Consensus for the prescription of depot antipsychotics]. / Recommandations Formalisées d'Experts de l'AFPBN : prescription des neuroleptiques et antipsychotiques d'action prolongée.

BACKGROUND: Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice. METHODS: The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia. RESULTS: LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors. CONCLUSION: A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed.

Epigenetic alterations of adenomatous polyposis coli (APC), retinoic acid receptor beta (RARß) and survivin genes in tumor tissues and voided urine of bladder cancer patients.

The CpG promoter methylation has been reported to occur frequently in bladder cancer. Moreover, analysis of gene methylation has been shown to be feasible from voided urine and can be detected with a high degree of sensitivity. The aim of this present study is to determine how methylation patterns of APC, RARβ and Survivin genes change during bladder carcinogenesis and to evaluate whether DNA methylation could be detected in urine sediment. Using the sensitive assay of MSP, we explored the promoter methylation status for the three genes in tumor specimens and urine sediment DNA from 32 bladder cancer patients. Methylation frequencies of the tested genes in tumor specimens were 100%, 75% and 84.4% for APC, RARβ and Survivin, respectively. Hypermethylation of APC was found in all pathological grades and stages of bladder cancer. More frequent promoter hypermethylation of RARβ and Survivin was observed in high grade tumors and the hypermethylation increased from low to high stages, but there was no significant correlation between stages/grades and hypermethylation of these two gene promoters. In order to investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status in urine samples of bladder cancer patients. Methylation of the tested genes in urine sediment DNA was detected in the majority of cases that were hypermethylated in tumor samples (93.7%) and the frequencies were 79.3% 70.8% and 96.3% for APC, RARβ and Survivin, respectively. Our results indicate that methylation of APC, RARβ and Survivin gene promoters is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancer.

Video self-confrontation as a therapeutic tool in schizophrenia: A randomized parallel-arm single-blind trial.

BACKGROUND: Lack of insight is a barrier to treating psychosis. Preliminary studies have suggested that showing people videos of their psychotic behaviour may improve personal insight. This clinical trial aimed to assess the effect of video self-confrontation. METHODS: Inpatients between 18 and 65 years old with schizophrenia or schizoaffective disorder were filmed upon admission to two psychiatric hospitals while experiencing acute psychosis. After stabilization, individuals were randomized 1:1 to the "self-video" group where they watched their own video or to the "no video" control group. The primary outcome was the Scale to assess Unawareness of Mental Disorder (SUMD) at 48 h by a blinded assessor. Secondary objectives included psychotic and depressive symptoms, medication adherence and functioning using the Functional Remission of General Schizophrenia. Patients were followed up for four months. RESULTS: 60 participants were randomized and the level of insight did not differ between groups at 48 h (p = 0.98). There was no impact on SUMD subscores or the other insight questionnaires at any timepoint, nor on psychopathology or medication adherence. At one month, the level of functioning of those in the "self-video" group (n = 23) was higher (61.8 vs 53.5, p = 0.02), especially concerning "Treatment" and "Daily life". No adverse effects were reported. After video self-confrontation, people expressed more positive than negative emotions and were less lost to follow-up. CONCLUSION: Video self-confrontation did not change levels of insight, but may have a therapeutic impact nonetheless, by improving levels of self-care and adherence to care, indicating that this innovative therapeutic tool requires further study. TRIAL REGISTRATION NUMBER: NCT02664129.

The need to consider mood disorders, and especially chronic mania, in cases of Diogenes syndrome (squalor syndrome).

We report the case of a 69 year-old female patient who was hospitalized for Diogenes syndrome, defined by marked self-neglect, social withdrawal and excessive hoarding, leading to squalor. Somatic causes were eliminated. Her personal history showed an eight-year depressive episode followed by a 20-year hypomanic episode without remission, followed by a persistent manic episode associated with Diogenes syndrome for four years. The Diogenes syndrome was successfully treated with mood stabilizers. Mood disorders - in particular chronic mania (i.e. a manic episode lasting more than two years) - should be considered in cases of Diogenes syndrome and in current classifications.

[US-guided transrectal drainage of prostatic abscesses]. / Aspiration échoguidée transrectale des abcès prostatiques.

Prostatic abscess is rare and most commonly occurs as a complication of acute prostatitis. Because of the wider use of antibiotics, the clinical presentation is becoming less typical. Diagnosis is useful for diagnosis. Based on a review of 3 cases, the authors report their experience with US-guided transrectal drainage of prostatic abscesses and review other therapeutic options.

[Renocolic fistula following abdominal trauma: a case study]. / Les fistules rénocoliques post-traumatiques : à propos d'une observation.

The renocolic fistula is a rare entity, which has occurred exceptionally in a traumatic not iatrogenic context, we report a case of renocolic fistula complicating penetrating abdominal trauma from a gunshot.

[Role of polyvidone-iodine ablation in the management of symptomatic renal cysts]. / Place de la ponction-sclérothérapie à la polyvidone-iodine dans le traitement des kystes rénaux simples symptomatiques.

OBJECTIVE: To assess prospectively the results of percutaneous sclerotherapy with povidone-iodine of symptomatic renal cysts in adults. METHODS: Fifty two patients were included in this study from august 2004 to november 2006. The operative indication was: pain (41 cases), urinary tract compression (8 cases), and very large cyst (3 cases). The preoperative assessment (site and dimensions of the cyst) always included ultrasonography. CT scan, for morphological assessment, was performed in 39 cases. RESULTS: The mean age of patients was 63 years (47-75 years). The mean diameter was 76 mm. The cysts were punctured in all the cases directly under local anaesthesia and guided by sonography. The procedure was very well tolerated in every case, with external drainage for 72 hours. Clinical regression was complete in 48 cases (92%), with total ultrasonographic disappearing of the cysts in 31 cases (60%) with a mean follow-up of 14 months (3-29 months). CONCLUSION: Percutaneous sclerotherapy with povidone-iodine is a safe, effective and reproducible treatment of symptomatic renal cysts in adults.

[Primitive neuroectodermal tumor (PNET) of the upper-urinary tract]. / Tumeur neuro-ectodermique primitive (TNEP) de la voie excrétrice supérieure.

Primitive neuroectodermal tumors (PNETs) are rare and aggressive malignant small round cell sarcomas. Primitive urogenital location of PNETs is rare and occurs most frequently in the kidney. PNETs of the upper-urinary tract are exceptional (only one case reported in the literature). Its diagnosis is almost postoperative within pathological study of the operatory specimen, supported by immunohistochemistry and cytogenetics. Treatment is similar in all to that of Ewing's sarcoma and involves surgery, chemotherapy and radiotherapy. We report a new case of upper-urinary tract PNET and discuss the diagnostic and therapeutic problems posed by this particular tumor.

Recurrence and mortality 1 year after hospital admission for non-fatal self-harm: a nationwide population-based study.

AIMS: A large number of people present each day at hospitals for non-fatal deliberate self-harm (DSH). Examination of the short-term risk of non-fatal recurrence and mortality at the national level is of major importance for both individual medical decision-making and global organisation of care. METHODS: Following the almost exhaustive linkage (96%) of two national registries in France covering 45 million inhabitants (i.e. 70% of the whole population), information about hospitalisation for DSH in 2008-2009 and vital status at 1 year was obtained. Individuals who died during the index hospital stay were excluded from analyses. RESULTS: Over 2 years, 136,451 individuals were hospitalised in medicine or surgery for DSH. The sample comprised 62.8% women, median age 38 in both genders, with two peaks at 16 and 44 years in women, and one peak at 37 years in men. The method used for DSH was drug overdose in 82.1% of cases. Admission to an intensive care unit occurred in 12.9%. Following index hospitalisation, 71.3% returned home and 23.7% were transferred to a psychiatric inpatient care unit. DSH recurrence during the following year occurred in 12.4% of the sample, within the first 6 months in 75.2%, and only once in 74.6%. At 1 year, 2.6% of the sample had died. The overall standardised mortality ratio was 7.5 but reached more than 20 in young adults. The causes were natural causes (35.7%), suicide (34.4%), unspecified cause (17.5%) and accident (12.4%). Most (62.9%) deaths by suicide occurred within the first 6 months following index DSH. Violent means (i.e. not drug overdose) were used in 70% of suicide cases. Concordance between means used for index DSH and for suicide was low (30% overall), except for drug overdose. Main suicide risk factors were older age, being male, use of a violent means at index DSH, index admission to an intensive care unit, a transfer to another medical department or to a psychiatric inpatient unit, and recurrence of DSH. However, these factors had low positive predictive values individually (below 2%). CONCLUSIONS: Non-fatal DSH represent frequent events with a significant risk of short-term recurrence and death from various causes. The first 6 months following hospital discharge appear to be a critical period. Specific short-term aftercare programs targeting all people with a DSH episode have to be developed, along other suicide prevention strategies.

Pathological outcomes and agressiveness of low-risk prostate cancer in Northern African men. / Resultados patológicos y agresividad del cáncer de próstata de bajo riesgo en los hombres del norte de África.

BACKGROUND: Northern African (NAf) men show a high incidence of advanced prostate cancer (PCa) at diagnosis. Several studies suggested the existence of ethnic differences in the PCa aggressiveness and this has led to some concerns related to the inclusion of some ethnic groups into active surveillance protocols. OBJECTIVE: To evaluate pathological outcomes and aggressiveness of low risk PCa treated by radical prostatectomy in a NAf ethnic group. SUBJECTS AND METHODS: Data of 147 NAfs, who underwent radical prostatectomy for low risk PCa diagnosed via a 12-core biopsy in 2 academic centers between 2011 and 2015, were reviewed retrospectively to assess rates of worse pathological outcomes defined as: Gleason score upgrade to at least 3+4, upstage to pT3a or higher or pN1, and positive surgical margins. RESULTS: Overall significant upstage and/or upgrade occurred in 20.2% and positive surgical margins occured in18.3%. In multivariate logistic regression analysis, independent variables that predicted for upstage and/or upgrade or positive surgical margins in the entire cohort were: NCCN risk group (low risk>very low risk), advanced age>60 years, PSA>6ng/ml, PSA density≥0.15, more than 2 positive cores in biopsy, more than 50% cancer involvement in positive cores, clinical stage (T2a>T1c) and UCSF-CAPRA-S score>3. CONCLUSIONS: Our study found that, at least pathologically, NAf men do not have more aggressive disease than Caucasians and African Americans in both low and very low risk PCa. Thus, we think that active surveillance is a suitable approach for selected patients since there is no definitive data that show a more aggressive natural history of PCa in NAf men.

Suicidal behaviors and the tryptophan hydroxylase gene.

BACKGROUND: To determine whether the tryptophan hydroxylase gene (ie, the gene that codes for the rate-limiting enzyme in the metabolic pathway of serotonin) may be a susceptibility factor for suicidal behavior. METHODS: Genotypic and allelic frequencies at a polymorphic Ava II restriction site were revealed with the use of the complementary DNA tryptophan hydroxylase probe C2-38 in 62 suicide attempters. The psychiatric characteristics of these suicide attempters were determined using the Schedule for Affective Disorders and Schizophrenia-Lifetime version with modification for the study of anxiety disorders, and these characteristics were compared with those in 52 healthy controls. RESULTS: No association between tryptophan hydroxylase and suicidal behavior was detected. CONCLUSION: The tryptophan hydroxylase gene was not a susceptibility factor for suicidal behaviors in the group of suicide attempters in this study.

Clozapine and metabolite concentrations during treatment of patients with chronic schizophrenia.

Results presented in this article are focused on the variability in pharmacokinetics. The purpose of this study was (1) to investigate intra- and interindividual variabilities of pharmacokinetic parameters of clozapine and its two main metabolites in plasma after multiple oral administration in 8 chronic schizophrenic patients (Study 1) and (2) to gain more information regarding plasma concentrations of these drugs after multiple doses in a group of 25 treatment-responsive patients (Study 2). Patients were treated with clozapine in fixed daily doses (given every 8-12 hours) between 200 and 900 mg. Plasma drug concentrations were determined by high-performance liquid chromatography. The mean volume of distribution and the total plasma clearance of clozapine, uncorrected for bioavailability, were 7 L/kg and 40.5 L/h, respectively. The terminal elimination half-lives averaged 10.5 hours for clozapine, 19.2 hours for norclozapine, and 8.6 hours for the N-oxide metabolite. Significant relationships were observed between clozapine and norclozapine (or clozapine N-oxide) plasma concentrations. Large inter- and intrapatient variations in pharmacokinetics were observed. Clozapine was generally well tolerated by the patients, with sedation, hypersialorrhea, and tiredness as the most common side effects encountered.

Idiopathic retroperitoneal fibrosis and ankylosing spondylitis. A new case report.

The case of a 52-year-old man with retroperitoneal fibrosis and ankylosing spondylitis is described. Inflammatory low back pain and acute renal insufficiency prompted a computed tomography scan of the abdomen with contrast agent injection. A fibrous sheath surrounding the aorta and attracting the ureters toward the midline was seen, strongly suggesting retroperitoneal fibrosis. The diagnosis of ankylosing spondylitis was based on the presence of inflammatory low back pain responsive to nonsteroidal anti-inflammatory drugs, syndesmophytes at the lumbar and cervical spine, bilateral sacroiliitis, and presence of the HLA-B27 antigen. Prednisone therapy in a daily dosage of 1 mg/kg induced a marked improvement. Only nine cases of concomitant retroperitoneal fibrosis and ankylosing spondylitis have been reported. These two conditions share similarities in some of the etiologic factors and anatomic localizations, suggesting that both may stem from a predisposition to fibrotic diseases.

Tricyclics and malignant syndrome.

A clinical and biological pattern similar to that of neuroleptic malignant syndrome is reported in a depressed patient treated with trimipramine, without any concomitant use of neuroleptics. The antidopaminergic properties of this drug, one of the tricyclic antidepressants, may account for this uncommon side effect.

Overdose with sustained-release lithium preparations.

Acute lithium intoxication is potentially lethal. Compared to conventional lithium preparations, sustained-release lithium formulations present specific problems for medical practice in the case of overdose. We report a case of intoxication with 8000 mg of sustained-release lithium carbonate preparation (Teralithe 400 LP(R)). Twenty-five hours after the ingestion, the patient was still asymptomatic, despite a serum level in the toxic range. After comparison of this case with reports found in the Medline database, we consider the clinical management of such cases.