HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder.

Schizophrenia (SZ) and bipolar disorders (BD) are severe mental illnesses that lack reliable biomarkers to guide diagnosis and management. As immune dysregulation is associated with these disorders, we utilized the immunoregulatory functions of the natural killer cell inhibitory HLA-E locus to investigate the relationships between HLA-E genetic and expression diversities with SZ and BD risk and severity. Four hundred and forty-four patients meeting DSM-IV criteria for SZ (N = 161) or BD (N = 283) were compared to 160 heathy controls (HC). Circulating levels of the soluble isoform of HLA-E molecules (sHLA-E) were measured and HLA-E*01:01 and HLA-E*01:03 variants genotyped in the whole sample. sHLA-E circulating levels were significantly higher in both SZ and in BD patients compared to HC (pc < 0.0001 and pc = 0.0007 for SZ and BD, respectively). High sHLA-E levels were also observed in stable SZ patients and in acute BD patients experiencing depressive episodes when comparisons were made between the acute and stable subgroups of each disorder. sHLA-E levels linearly increased along HLA-E genotypes (p = 0.0036). In conclusion, HLA-E variants and level may have utility as diagnostic biomarkers of SZ and BD. The possible roles of HLA diversity in SZ and BD etiology and pathophysiology are discussed.

Clinical Pharmacy in Psychiatry: Towards Promoting Clinical Expertise in Psychopharmacology.

Although clinical pharmacy is a discipline that emerged in the 1960s, the question of precisely how pharmacists can play a role in therapeutic optimization remains unanswered. In the field of mental health, psychiatric pharmacists are increasingly involved in medication reconciliation and therapeutic patient education (or psychoeducation) to improve medication management and enhance medication adherence, respectively. However, psychiatric pharmacists must now assume a growing role in team-based models of care and engage in shared expertise in psychopharmacology in order to truly invest in therapeutic optimization of psychotropics. The increased skills in psychopharmacology and expertise in psychotherapeutic drug monitoring can contribute to future strengthening of the partnership between psychiatrists and psychiatric pharmacists. We propose a narrative review of the literature in order to show the relevance of a clinical pharmacist specializing in psychiatry. With this in mind, herein we will address: (i) briefly, the areas considered the basis of the deployment of clinical pharmacy in mental health, with medication reconciliation, therapeutic education of the patient, as well as the growing involvement of clinical pharmacists in the multidisciplinary reflection on pharmacotherapeutic decisions; (ii) in more depth, we present data concerning the use of therapeutic drug monitoring and shared expertise in psychopharmacology between psychiatric pharmacists and psychiatrists. These last two points are currently in full development in France through the deployment of Resource and Expertise Centers in PsychoPharmacology (CREPP in French).

Enhancing the role played by clinical pharmacists in psychiatric settings to better integrate clinical psychopharmacology into the decision-making process.

The importance of clinical psychopharmacological knowledge for modern psychiatric care is both well-established and underdeveloped. Although psychiatric pharmacists are identified as experts in psychopharmacotherapy based on pharmacists' overall expertise in pharmacotherapy, in real-life health settings, such is not necessarily the case. As a matter of fact, (1) pharmacists' real expertise in pharmacotherapy is mainly seen as useful to patients (as part of therapeutic education), (2) pharmacists' practice methods are usually circumscribed to the framework of quality processes (e.g. comprehensive medication management) which are not particularly useful to clinicians who have a greater need for pharmacotherapeutic skills, (3) the difficulties in terms of collaboration between pharmacists and physicians are well-known. We describe here the implementation of an alternative system of pharmacotherapy counselling inspired by case by cases in which the remote expertise of pharmacists in psychopharmacology guided prescribers towards the implementation of recommendations from the literature. This shared decision-making process integrates both the clinical elements provided by the psychiatrist and the pharmacotherapeutic information provided by the clinical psychopharmacist, to promote evidence-based medicine (algorithmic data in recommendations) and tailor-made solutions (drug-drug and drug-disease interactions) for patients. In our experience, the success of such an initiative is likely to promote the development of clinical psychopharmacology in psychiatric settings. Importantly, within this framework, the pharmacovigilance unit and psychopharmacologist are useful resources to guide the decision-making process of the pharmacist-psychiatrist duo.

Higher level of systemic C-reactive protein is independently predictive of coronary heart disease in older community-dwelling adults: the three-city study.

OBJECTIVES: To assess the association between systemic C-reactive protein (CRP) and incident coronary heart disease (CHD) in community-dwelling elderly people. DESIGN: A French population-based multicenter prospective cohort study. SETTING: Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast. PARTICIPANTS: After 4 years of follow-up, a case-cohort study was designed including 1,004 subjects randomly selected from the initial cohort of 9,294 subjects free of CHD at baseline and 174 subjects who developed first CHD events during follow-up. MEASUREMENTS: Hazard ratios (HRs) were estimated using a Cox proportional hazard model adapted for the case-cohort design using a CRP level less than 1 mg/L as the reference category. RESULTS: Of the random sample, 24.3% had a CRP level less than 1.0 mg/L, 45.8% had a CRP level of 1.0 to 2.9 mg/L, and 29.9% had a CRP level of 3.0 to 10.0 mg/L. The HRs for CHD, adjusted for age, sex, and study center, were 1.69 (95% confidence interval (CI)=1.04-2.75) for CRP from 1.0 to 2.9 mg/L and 2.32 (95% CI=1.41-3.82) for CRP from 3.0 to 10.0 mg/L (P for trend <.001). After additional adjustment for smoking, body mass index, diabetes mellitus, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, statin use, and antihypertensive treatment, a baseline CRP of 3.0 to 10.0 mg/L remained associated with risk of CHD (HR=1.87, 95% CI=1.09-3.25), although CRP did not improve the discriminative ability of a predicting model based on traditional risk factors (receiver operating characteristic curves from 0.740 to 0.749). CONCLUSION: CRP is an independent CHD risk marker but does not improve CHD risk prediction in community-dwelling elderly people.

[Patients' perception of information received when a complementary medical examination is prescribed]. / Perception par les patients de l'information reçue lors d'un examen complémentaire.

Medical doctors are required to provide information to their patients regarding their medical procedures according to the law on patient information enacted on March 4, 2002. The objective of this study was to assess patients' awareness and satisfaction with respect to their perception of information obtained prior to or during a medical examination. A self-descriptive patient survey was conducted at the Groupe Hospitalier of Pitié-Salpêtrière in 2005 for this purpose. Data were collected at three distinct moments using a standard questionnaire. 147 patients were interviewed (101 had received and MRI and 46 a bronchoscopy). Twenty percent of the participants reported that they had not been provided with any specific medical or paramedical information before the examination and 4% had received no information at all. Health professionals must ensure that information is given to their patients in a manner that takes into account their expectations and responds to their concerns before a medical procedure is performed in order to improve its delivery and its intrinsic quality.

Excessive heart rate increase during mild mental stress in preparation for exercise predicts sudden death in the general population.

AIMS: The aim of this study involves the early identification, among apparently healthy individuals, of those at high risk for sudden cardiac death. We tested the hypothesis that individuals who respond to mild mental stress in preparation for exercise test with the largest heart rate increases might be at highest risk. METHODS AND RESULTS: Data from 7746 civil servants participating in the Paris Prospective Study I, followed-up for 23 years, allowed to compare heart rate changes between rest and mild mental stress (preparation prior to an exercise test) between subjects who suffered sudden cardiac death (n = 81), non-sudden (n = 129) coronary death, or death from any cause (n = 1306). The mean heart rate increase during mild mental stress was 8.9 +/- 10.8 b.p.m. Risk of sudden cardiac death increased progressively with heart rate increase during mental stress and the relative risk of the third vs. the first tertile was 2.09 (95% confidence interval, 1.13-3.86) after adjustment for confounders. This relationship was not observed for non-sudden coronary death. CONCLUSION: An important heart rate increase produced by a mild mental stress predicts long-term risk for sudden cardiac death. Heart rate changes before an exercise test may provide a simple tool for risk stratification.

Postmenopausal hormone therapy and cardiovascular disease: an overview of main findings.

Cardiovascular disease has emerged as a leading cause of death in women. In recent years, significant attention has been paid to the potential benefits of hormone therapy on chronic diseases such as cardiovascular disease. Large prevention trials failed to confirm the cardioprotective effect of estrogen. The divergent findings from observational and randomized clinical studies are summarized and reasons for the different results are postulated. Use of estrogen alone or estrogen opposed with progestins is not indicated for the prevention of cardiovascular disease and may even increase the risk of stroke. Oral estrogen increases venous thromboembolism events. Recent data suggest that transdermal estrogens are safe with respect to venous thromboembolism. Current data have limited ability to investigate the wide variety of hormone treatments available. Clinical research should be continued to assist patients and clinicians in making treatment decisions on the basis of an individual's benefits and risks.

Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration.

BACKGROUND: Oral estrogen increases the risk of venous thromboembolism (VTE) in postmenopausal women, particularly in those with a prothrombotic mutation. Transdermal estrogen may be safe with respect to VTE. We investigated the impact of the route of estrogen administration on the association between a prothrombotic mutation (factor V Leiden or prothrombin G20210A mutation) and VTE risk. METHODS AND RESULTS: We performed a multicenter case-control study of VTE among postmenopausal women who were enrolled in 1999 through 2004 at 7 clinical centers in France. We recruited 235 consecutive patients with a first documented episode of idiopathic VTE and 554 controls. Factor V Leiden was associated with a 3.4-fold-increased risk of VTE (95% confidence interval [CI], 2.0 to 5.8), and a prothrombin mutation was associated with a 4.8-fold-increased risk of VTE (95% CI, 2.5 to 9.4). Oral but not transdermal estrogen was associated with an increased risk of VTE (odds ratio [OR], 4.3; 95% CI, 2.6 to 7.2; and OR, 1.2; 95% CI, 0.8 to 1.7, respectively). After adjustment for potential confounding factors, the combination of either factor V Leiden or prothrombin G20210A mutation and oral estrogen gave a 25-fold-increased risk of VTE compared with nonusers without mutation (95% CI, 6.9 to 95.0). However, the risk for women with prothrombotic mutation using transdermal estrogen was similar to that of women with a mutation who were not using estrogen (OR, 4.4; 95% CI, 2.0 to 9.9; and OR, 4.1; 95% CI, 2.3 to 7.4, respectively). CONCLUSIONS: In contrast to oral estrogen, transdermal estrogen does not confer additional risk on women who carry a prothrombotic mutation. The safety of transdermal estrogen has to be confirmed in randomized trials.

Dose-dependent resorption of quinine after intrarectal administration to children with moderate Plasmodium falciparum malaria.

The pharmacokinetics of increasing doses of an intrarectal Cinchona alkaloid combination containing 96.1% quinine, 2.5% quinidine, 0.68% cinchonine, and 0.67% cinchonidine (Quinimax) was compared to that of parenteral regimens in 60 children with moderate malaria. Quinine exhibited a nonlinear pharmacokinetics, suggesting a saturation of rectal resorption. When early rejections appeared, blood quinine concentrations decreased by 30 to 50% and were restored by an immediate half-dose administration of the drug. Rectal administration of doses of 16 or 20 mg/kg of body weight led to concentration-time profiles in blood similar to those of parenteral regimens and could be an early treatment of childhood malaria.