Training of interviewers in the utilization of standardized questionnaires in psychiatry: studies realized with the Present State Examination (PSE)]

Interview questionnaires offer more validity than self-administered format in exploring psychopathological or psychosocial phenomena of interest in psychiatric research. If used, special care needs to be paid to interviewers' training and ensuring that they maintain their reliability. No widespread training standards exist and each schedule may carry its own procedure. Our aims are to indicate how we trained interviewers with the French version of the Present State Examination (Wing, Cooper and Sartorius, 1974) and how we checked and kept acceptable interraters reliability during one study. We will provide data on the interraters reliability during the training and the study, as well as the test-retest reliability. These results will be used to support some guidelines when using this sort of psychiatric research questionnaires in order to ensure comparability both within the study and between studies.     

Improving Mutation Screening in Familial Hematuric Nephropathies through Next Generation Sequencing

Alport syndrome is an inherited nephropathy associated with mutations in genes encoding type IV collagen chains present in the glomerular basement membrane. COL4A5 mutations are associated with the major X-linked form of the disease, and COL4A3 and COL4A4 mutations are associated with autosomal recessive and dominant forms (thought to be involved in 15% and 1%–5% of the families, respectively) and benign familial hematuria. Mutation screening of these three large genes is time-consuming and expensive. Here, we carried out a combination of multiplex PCR, amplicon quantification, and next generation sequencing (NGS) analysis of three genes in 101 unrelated patients. We identified 88 mutations and 6 variations of unknown significance on 116 alleles in 83 patients. Two additional indel mutations were found only by secondary Sanger sequencing, but they were easily identified retrospectively with the web-based sequence visualization tool Integrative Genomics Viewer. Altogether, 75 mutations were novel. Sequencing the three genes simultaneously was particularly advantageous as the mode of inheritance could not be determined with certainty in many instances. The proportion of mutations in COL4A3 and COL4A4 was notably high, and the autosomal dominant forms of Alport syndrome appear more frequently than reported previously. Finally, this approach allowed the identification of large COL4A3 and COL4A4 rearrangements not described previously. We conclude that NGS is efficient, reduces screening time and cost, and facilitates the provision of appropriate genetic counseling in Alport syndrome.     

Patient profiles as organizing HIV clinicians’ ART adherence management: a qualitative analysis

The effectiveness of antiretroviral therapy (ART) depends on optimal clinical management and patient adherence. Little is known about patient characteristics that clinicians consider in the management of ART adherence. Exploring this issue, five focus groups were conducted with 31 HIV-clinicians from across France. A qualitative typological analysis suggests that clinician management of patient adherence is based on characteristics that coalesce into seven patient profiles. For the “passive” patient, described as taking ART exactly as prescribed without questioning their doctor’s expertise, a directive and simple management style was preferred. The “misleading” patient is characterized as concerned with social desirability and as reporting no adherence difficulties for fear of displeasing their doctor. If clinical outcomes are suboptimal, the clinicians’ strategy is to remind them of the importance of open patient-clinician communication. The “stoic” patient is described as requesting and adequately taking the most potent ART available. Here, clinicians emphasize assessment of side effects, which the patient may minimize. The “hedonistic” patient’s festive lifestyle and sexual risk-taking are seen as compromising adherence; with them, clinicians stress the patient’s responsibility for their own health and that of their sexual partners. The “obsessive” patient is portrayed as having an irrational fear of ART failure and an inability to distinguish illusory from genuine adherence barriers. With this patient, clinicians seek to identify the latter. The “overburdened” patient is recognized as coping with life priorities that interfere with adherence and, with them, a forgiving ART is favored. The “underprivileged” patient is presented as having limited education, income and housing. In this case, clinicians seek to improve the patient’s living conditions and access to care. These results shed light on HIV clinicians’ ART adherence management. The value of these profiles for HIV care and patients should be investigated.     

The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.     

Children with conducts disorder and using psychoeducational services: a social, psychological and family portrait

Contemporary studies suggest that most of the children who manifest conducts disorder also present personal as well as family problems. This is particularly true for children whose disorder is precocious. The identification of personal characteristics as well as social and family risk and protection factors associated with children with such problems are of great use for intervention planning and service organization for them and their families in Québec. In consequence, the objectives of this study are to identify the social, family and psychological factors that characterize children presenting conducts disorder. To do so, 62 children in treatment between the ages of 7 and 12 and with a diagnosis of conducts disorder are compared with 36 children of the same age without such diagnosis. Results show that children with conduct problems come from less stable and cohesive families as well as a lower socio-economic level. Moreover, their network of social support is less developed. The study reveals that the parents of children with conducts disorder use punishment more often. Finally, the research demonstrates that the children of this group have a much higher probability of presenting an exteriorized disorder (66 %) than the children of the other group (8 %). All these distinctive characteristics allows to correctly classify 93,8 % of the children of this study in the 2 groups. The results indicate the need to improve the parents'educational practices, increase the child's social network as well as reduce the conducts of opposition and inattention of the child. Finally, the complexity of the problems raised with the child and families commands a concerted professional intervention.     

Regulation of calcium channel expression in neonatal myocytes by catecholamines.

Expression of the dihydropyridine (DHP) receptor (alpha 1 subunit of L-type calcium channel) in heart is regulated by differentiation and innervation and is altered in congestive heart failure. We examined the transmembrane signaling pathways by which norepinephrine regulates DHP receptor expression in cultured neonatal rat ventricular myocytes. Using a 1.3-kb rat cardiac DHP receptor probe, and Northern analysis quantified by laser densitometry, we found that norepinephrine exposure produced a 2.2-fold increase in DHP receptor mRNA levels at 2 h followed by a decline to 50% of control at 4-48 h (P < 0.02). The alpha-adrenergic agonist phenylephrine and a phorbol ester produced a decline in mRNA levels (8-48 h). The beta-adrenergic agonist isoproterenol and 8-bromo-cAMP produced a transient increase in mRNA levels. After 24 h of exposure to isoproterenol, 3H-(+)PN200-110 binding sites increased from 410 +/- 8 to 539 +/- 39 fmol/mg (P < 0.05). The number of functional calcium channels, estimated by whole-cell voltage clamp experiments, was also increased after 24 h of exposure to isoproterenol. Peak current density (recordings performed in absence of isoproterenol) increased from -10.8 +/- 0.8 (n = 23) to -13.9 +/- 1.0 pA/pF (n = 27) (P < 0.01). Other characteristics of the calcium current (voltage for peak current, activation, and inactivation) were unchanged. Exposure for 48 h to phenylephrine produced a significant decline in peak current density (P < 0.01). We conclude that beta -adrenergic transmembrane signaling increases DHP receptor mRNA and number of functional calcium channels and that alpha - adrenergic transmembrane signaling produces a reciprocal effect. Regulation of cardiac calcium channel expression by adrenergic pathways may have physiological and pathophysiological importance.     

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single‐centre study

Aim. Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. Methods. We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste‐Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow‐up visit. Results. We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2–20.7 years) at the initiation of treatment. The average length of follow‐up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow‐up visit, respectively. One became seizure‐free. Adverse effects were reported in 11 patients and none were severe. Responders and non‐responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). Conclusion. Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.     

The associations among economic hardship, caregiver psychological distress, disease activity, and health-related quality of life in children with juvenile idiopathic arthritis

Purpose

To examine the associations among caregiver perceived economic hardship, psychological distress, children??s disease activity, and health-related quality of life (HRQOL) in children with juvenile idiopathic arthritis (JIA).

Methods

Caregivers of 182 children with JIA (ages 2?C18) attending the rheumatology clinics at the Montreal Children??s Hospital and the British Columbia??s Children Hospital completed a series of questionnaires on perceived financial hardship, caregiver psychological distress, and children??s HRQOL at baseline, 6 and 12?months. Clinical information such as disease activity was obtained from medical charts. Statistical models were used to look at the significance of several factors of interest while controlling for possible confounders.

Results

Higher caregiver perceived economic hardship [(???=?0.03, 95% CI?=?0.005, 0.06), P?=?0.02], psychological distress [(???=?0.02, 95% CI?=?0.006, 0.03), P?=?0.004], and higher children??s disease activity [(???=?0.11, 95% CI?=?0.07, 0.15), P?Conclusions Findings suggest that caregiver financial hardship and psychological distress as well as children??s disease activity may impact children??s HRQOL. By providing psychological help to parents, offering information regarding financial resources in the community and by ensuring disease control, especially when the disease is severe, health providers may improve children??s health outcomes.     

Acute anuric renal failure: a complication of combined thrombolytic and antithrombotic therapy

Thrombolytic agents are routinely given to patients with acute myocardial infarction, often in combination with heparin. Genitourinary hemorrhage is an uncommon adverse effect of systemic thrombolysis, and acute azotemic complications are distinctly rare. We describe a case of genitourinary hemorrhage after combined thrombolytic and antithrombotic therapy leading to acute bilateral ureteral obstruction and then briefly review renal complications of systemic thrombolysis.