Hyperfrontality and hypoconnectivity during refreshing in schizophrenia.

Anomalous activations of the prefrontal cortex (PFC) and posterior cerebral areas have been reported in previous studies of working memory in schizophrenia. Several interpretations have been reported: e.g., neural inefficiency, the use of different strategies and differences in the functional organization of the cerebral cortex. To better understand these abnormal activations, we investigated the cerebral bases of a working memory component process, namely refreshing (i.e., thinking briefly of a just-activated representation). Fifteen patients with schizophrenia and 15 control subjects participated in this functional magnetic resonance imaging (fMRI) study. Participants were told that whenever they saw a word on the screen, they had to read it silently to themselves (read and repeat conditions), and when they saw a dot, they had to think of the just-previous word (refresh condition). The refresh condition (in comparison with the read condition) was associated with significantly increased activation in the left inferior frontal gyrus and significantly decreased connectivity within the prefrontal cortex and between the prefrontal and parietal cortices in patients with schizophrenia in comparison with control subjects. These results suggest that prefrontal dysfunctions in schizophrenia might be related to a defective ability to initiate (rather than to execute) specific cognitive processes.

Oral cancer treatments and adherence: medication event monitoring system assessment for capecitabine

Background: Oncological treatments are traditionally administered via intravenous injection by qualified personnel. Oral formulas which are developing rapidly are preferred by patients and facilitate administration however they may increase non-adherence. In this study 4 common oral chemotherapeutics are given to 50 patients, who are still in the process of inclusion, divided into 4 groups. The aim is to evaluate adherence and offer these patients interdisciplinary support with the joint help of doctors and pharmacists. We present here the results for capecitabine. Materials and Methods: The final goal is to evaluate adhesion in 50 patients split into 4 groups according to oral treatments (letrozole/exemestane, imatinib/sunitinib, capecitabine and temozolomide) using persistence and quality of execution as parameters. These parameters are evaluated using a medication event monitoring system (MEMS®) in addition to routine oncological visits and semi-structured interviews. Patients were monitored for the entire duration of treatment up to a maximum of 1 year. Patient satisfaction was assessed at the end of the monitoring period using a standardized questionary. Results: Capecitabine group included 2 women and 8 men with a median age of 55 years (range: 36−77 years) monitored for an average duration of 100 days (range: 5-210 days). Persistence was 98% and quality of execution 95%. 5 patients underwent cyclic treatment (2 out of 3 weeks) and 5 patients continuous treatment. Toxicities higher than grade 1 were grade 2−3 hand-foot syndrome in 1 patient and grade 3 acute coronary syndrome in 1 patient both without impact on adherence. Patients were satisfied with the interviews undergone during the study (57% useful, 28% very useful, 15% useless) and successfully integrated the MEMS® in their daily lives (57% very easily, 43% easily) according to the results obtained by questionary at the end of the monitoring period. Conclusion: Persistence and quality of execution observed in our Capecitabine group of patients were excellent and better than expected compared to previously published studies. The interdisciplinary approach allowed us to better identify and help patients with toxicities to maintain adherence. Overall patients were satisfied with the global interdisciplinary follow-up. With longer follow up better evaluation of our method and its impact will be possible. Interpretation of the results of patients in the other groups of this ongoing trial will provide us information for a more detailed analysis.

Plus de femmes que d'hommes VIH positifs sont réferees à une consultation d'adhésion thérapeutique [More HIV-positive women are referred to a medication adherence clinic than men].

HIV-positive patients with antiretroviral medication adherence issues are referred to an outpatient adherence clinic. Surprisingly, two-third of referred patients are women although more than 60% of the patients at the Infectious Disease Outpatient service are men. Women seem to be referred because of specific social factors: children at home, black sub-Saharan ethnicity, difficulties in medication and disease management due to stigmatization. Literature is poor and controversial and it is not possible to conclude whether medication adherence varies with gender. However, recent data seem to show that reasons for nonadherence vary according to gender.

Toward an integration of spirituality and religiousness into the psychosocial dimension of schizophrenia.

OBJECTIVE: Spirituality and religiousness have been shown to be highly prevalent among patients with schizophrenia. However, clinicians are rarely aware of the importance of religion and understand little of the value or difficulties it presents to treatment. This study aimed to assess the role of religion as a mediating variable in the process of coping with psychotic illness. METHOD: Semistructured interviews about religious coping were conducted with a sample of 115 outpatients with psychotic illness. RESULTS: For some patients, religion instilled hope, purpose, and meaning in their lives (71%), whereas for others, it induced spiritual despair (14%). Patients also reported that religion lessened (54%) or increased (10%) psychotic and general symptoms. Religion was also reported to increase social integration (28%) or social isolation (3%). It may reduce (33%) or increase (10%) the risk of suicide attempts, reduce (14%) or increase (3%) substance use, and foster adherence to (16%) or be in opposition to (15%) psychiatric treatment. CONCLUSIONS: Our results highlight the clinical significance of religion in the care of patients with schizophrenia. Religion is neither a strictly personal matter nor a strictly cultural one. Spirituality should be integrated into the psychosocial dimension of care. Our results suggest that the complexity of the relationship between religion and illness requires a highly sensitive approach to each unique story.

First episode schizophrenia and schizoaffective disorder: A psychiatric nosology

A nosological issue that has yet to be resolved relates to the diagnostic and clinical overlap of schizophrenia and schizoaffective disorder. Thus, the aim of this study was to compare, within a treated epidemiological cohort of first episode patients, the clinical characteristics of patients with schizophrenia (FES) or schizoaffective disorder (FESA). Medical fi le audit methodology was employed to collect information on 704 first episode psychosis patients (FEP), among which 283 patients had a fi nal diagnosis of FES and 64 patients with a fi nal diagnosis of FESA. These patients were treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. Patients with FES were signifi cantly more likely to have a longer prodrome (P = .020), longer duration of untreated psychosis (P < .001), and earlier age of onset (P = .004) compared to FESA. At service entry, FESA patients had more severe levels of psychopathology (P = .020), which was due to the presence of manic symptoms (P < .001); consequently, requiring a greater number of inpatient admissions (P = .017). At discharge, depressive symptoms were more severe in those with FESA (P = .011). There are signifi cant differences in the phenomenology of schizophrenia and schizoaffective disorder during early illness course; supporting the notion that these are two discernable disorders.

Safety-seeking behaviours and verbal auditory hallucinations in schizophrenia.

Verbal auditory hallucinations can have a strong impact on the social and professional functioning of individuals diagnosed with schizophrenia. The safety-seeking behaviours used to reduce the threat associated with voices play a significant role in explaining the functional consequences of auditory hallucinations. Nevertheless, these safety-seeking behaviours have been little studied. Twenty-eight patients with schizophrenia and verbal auditory hallucinations were recruited for this study. Hallucinations were evaluated using the Psychotic Symptom Rating Scale and the Belief About Voice Questionnaire and safety behaviours using a modified version of the Safety Behaviour Questionnaire. Our results show that the vast majority of patients relies on safety behaviours to reduce the threat associated with voices. This reliance on safety behaviours is mostly explained by beliefs about origin of voices the omnipotence attributed to hallucinations and the behavioural and emotional reactions to the voices. Safety-seeking behaviours play an important role in maintaining dysfunctional beliefs with respect to voices. They should be better targeted within the cognitive and behavioural therapies for auditory hallucinations.

Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia.

Abstract Genetic studies have shown an association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the glutamate cysteine ligase (GCL), the key enzyme for glutathione (GSH) synthesis. The present study was aimed at analyzing the influence of a GSH dysregulation of genetic origin on plasma thiols (total cysteine, homocysteine, and cysteine-glycine) and other free amino acid levels as well as fibroblast cultures GSH levels. Plasma thiols levels were also compared between patients and controls. As compared with patients with a low-risk GCLC GAG TNR genotype, patients with a high-risk genotype, having an impaired GSH synthesis, displayed a decrease of fibroblast GSH and plasma total cysteine levels, and an increase of the oxidized form of cysteine (cystine) content. Increased levels of plasma free serine, glutamine, citrulline, and arginine were also observed in the high-risk genotype. Taken together, the high-risk genotypes were associated with a subgroup of schizophrenia characterized by altered plasma thiols and free amino acid levels that reflect a dysregulation of redox control and an increased susceptibility to oxidative stress. This altered pattern potentially contributes to the development of a biomarker profile useful for early diagnosis and monitoring the effectiveness of novel drugs targeting redox dysregulation in schizophrenia. Antioxid. Redox Signal. 15, 2003-2010.

Glutathione Precursor, N-Acetyl-Cysteine, Modulates EEG Synchronization in Schizophrenia Patients

Background: Glutathione (GSH) dysregulation at the gene, protein and functional levels observed in schizophrenia patients, and schizophrenia-like anomalies in GSH deficit experimental models, suggest that genetic glutathione synthesis impairments represent one major risk factor for the disease (Do et al., 2009). In a randomized, double blind, placebo controlled, add-on clinical trial of 140 patients, the GSH precursor N-Acetyl-Cysteine (NAC, 2g/day, 6 months) significantly improved the negative symptoms and reduced sideeffects due to antipsychotics (Berk et al., 2008). In a subset of patients (n=7), NAC (2g/day, 2 months, cross-over design) also improved auditory evoked potentials, the NMDA-dependent mismatch negativity (Lavoie et al, 2008). Methods: To determine whether increased GSH levels would modulate the topography of functional brain connectivity, we applied a multivariate phase synchronization (MPS) estimator (Knyazeva et al, 2008) to dense-array EEGs recorded during rest with eyes closed at the protocol onset, the point of crossover, and at its end. Results: The whole-head imaging revealed a specific synchronization landscape in NAC compared to placebo condition. In particular, NAC increased MPS over frontal and left temporal regions in a frequency-specific manner. The topography and direction of MPS changes were similar and robust in all 7 patients. Moreover, these changes correlated with the changes in the Liddle's score of disorganization, thus linking EEG synchronization to the improvement of the clinical picture. Conclusions: The data suggest an important pathway towards new therapeutic strategies that target GSH dysregulation in schizophrenia. They also show the utility of MPS mapping as a marker of treatment efficacy.

Using the costs of drug therapy to screen patients for a community pharmacy-based medication review program

Objectives: To measure the positive predictive value (PPV) of the cost of drug therapy (threshold = 2000 Swiss francs [CHF], US$1440, <euro>1360) as a screening criterion for identifying patients who may benefit from medication review (MR). To describe identified drug-related problems (DRPs) and expense problems (EPs), and to estimate potential savings if all recommendations were accepted. Setting Five voluntary Swiss community pharmacies. Methods: Of 12,680 patients, 592 (4.7%) had drug therapy costs exceeding 2000 CHF over a six-month period from July 1 to December 31, 2002. This threshold limit was set to identify high-risk patients for DRPs and EPs. Three pharmacists consecutively conducted a medication review based on the pharmaceutical charts of 125 sampled patients who met the inclusion criterion. Main outcome measure: The PPV of a threshold of 2000 CHF for identifying patients who might benefit from a MR: true positives were patients with at least one DRP, while false positives were patients with no DRP. Results: The selection based on this criterion had a PPV of 86% for detecting patients with at least one DRP and 95% if EPs were also considered. There was a mean of 2.64 (SD = 2.20) DRPs per patient and a mean of 2.14 (SD = 1.39) EPs per patient. Of these patients, 90% were over 65 years old or were treated with at least five chronic medications, two common criteria for identifying patients at risk of DRPs. The main types of DRPs were drug-drug interactions, compliance problems and duplicate drugs. Mean daily drug cost per patient was CHF 14.87 (US$10.70, <euro>10.10). A potential savings of CHF 1.67 (US$1.20, <euro>1.14) per day (11%) was estimated if all recommendations to solve DRPs and EPs suggested herein were implemented. Conclusion: Further studies should investigate whether the potential benefit of medication reviews in preventing DRPs and containing costs in this patient group can be confirmed in a real practice environment. [Authors]

Adhésion thérapeutique du patient chronique: des concepts a la prise en charge ambulatoire [Medication adherence in chronic patients: from its concepts to its management in primary care].

Medication nonadherence is common and its determinants are diverse. Adherence is influenced by many parameters, such as patient's self-efficacy, knowledge of health risk, outcome expectations, benefits of change, and barriers and facilitators. The sociocognitive theory helps professionals to structure their approach and to support patients in managing their treatment. Professionals need skills and time, and benefit from coordination in care, in particular between physicians and pharmacists. This article presents the key elements of a medication adherence program as well as tools and some useful questions.