Paliperidone extended-release tablets in patients with recently diagnosed schizophrenia

Aim: Effective early and persistent antipsychotic treatment in recently diagnosed schizophrenia may positively impact long-term outcomes. Paliperidone extended-release (ER) was assessed in this population. Methods: Post hoc analysis of pooled data from three 6-week, double-blind (DB), placebo-controlled, and three 1-year open-label (OL) studies of paliperidone ER in schizophrenia patients. Data stratified by time since diagnosis (≤3 vs. >3 years). Results: At DB (n = 1193) and OL baselines (n = 744), 259 (21.9%) and 188 (25.3%) patients were diagnosed ≤3 years. At DB end point, both populations improved with paliperidone ER versus placebo on Positive and Negative Syndrome Scale (PANSS) total, Clinical Global Impressions–Severity and Personal and Social Performance (PSP) scale scores (all P < 0.05). At OL end point, there were significant improvements from DB baseline in both populations on these scales (P < 0.0001), with greater improvement in the ≤3-year population on PANSS total (P < 0.001) and PSP (P < 0.001) scores. During DB treatment, only the ≤3-year population reported adverse events (AEs) in ≥5% (placebo-adjusted rate) of subjects receiving paliperidone ER: akathisia, extrapyramidal disorder not otherwise specified and somnolence. During OL treatment, akathisia and somnolence occurred more frequently (≥5%) in the ≤3- versus >3-year population. OL study completion rates were 51.1% in ≤3-year, and 48.2% in >3-year subjects. Conclusions: Paliperidone ER significantly improved symptoms and functioning in schizophrenia patients, regardless of time since diagnosis. Recently diagnosed patients who continued treatment exhibited greater symptom reduction and functional benefit over the long term. Results also suggest that these patients may be more susceptible to certain AEs.     

Risperidone in the management of disruptive behavior disorders

Disruptive behavior disorders (DBDs) represent a spectrum of disorders, including conduct disorder and oppositional-defiant disorder. The atypical antipsychotic risperidone may be useful for the management of patients with DBDs. Clinical data on risperidone have demonstrated efficacy and satisfactory tolerability in improving angry, aggressive, self-injurious, and disruptive symptoms and behavior in children with pervasive developmental disorders and mood disorders. This paper reviews the results of recent studies that have evaluated the efficacy and safety of risperidone in the treatment of pediatric patients with DBDs. Because concerns have been raised regarding the safety of atypical antipsychotic treatment in pediatric patients, this paper further evaluates safety risks by presenting newly completed analyses of movement disorders, prolactin concentrations, body weight, and cognitive function data from short- and long-term studies in this patient population. A comprehensive review of all of the findings suggests that risperidone is an effective and well-tolerated treatment option for children and adolescents with DBDs. As with all antipsychotics, practitioners should monitor young patients' growth, weight, sexual maturation, and metabolic parameters.     

Analysis of the isoprenoid biosynthesis pathways in Listeria monocytogenes reveals a role for the alternative 2-C-methyl-D-erythritol 4-phosphate pathway in murine infection

Most bacteria synthesize isoprenoids through one of two essential pathways which provide the basic building block, isopentyl diphosphate (IPP): either the classical mevalonate pathway or the alternative non-mevalonate 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. However, postgenomic analyses of the Listeria monocytogenes genome revealed that this pathogen possesses the genetic capacity to produce the complete set of enzymes involved in both pathways. The nonpathogenic species Listeria innocua naturally lacks the last two genes (gcpE and lytB) of the MEP pathway, and bioinformatic analyses strongly suggest that the genes have been lost through evolution. In the present study we show that heterologous expression of gcpE and lytB in L. innocua can functionally restore the MEP pathway in this organism and confer on it the ability to induce Vgamma9 Vdelta2 T cells. We have previously confirmed that both pathways are functional in L. monocytogenes and can provide sufficient IPP for normal growth in laboratory media (M. Begley, C. G. Gahan, A. K. Kollas, M. Hintz, C. Hill, H. Jomaa, and M. Eberl, FEBS Lett. 561:99-104, 2004). Here we describe a targeted mutagenesis strategy to create a double pathway mutant in L. monocytogenes which cannot grow in the absence of exogenously provided mevalonate, confirming the requirement for at least one intact pathway for growth. In addition, murine studies revealed that mutants lacking the MEP pathway were impaired in virulence relative to the parent strain during intraperitoneal infection, while mutants lacking the classical mevalonate pathway were not impaired in virulence potential. In vivo bioluminescence imaging also confirmed in vivo expression of the gcpE gene (MEP pathway) during murine infection.     

The Jailbreak Health Project--incorporating a unique radio programme for prisoners

Several studies in NSW have identified prisoners to be at high risk for blood borne viruses. The prevalence of hepatitis C among men in NSW correctional centres is 40% and over 60% among women. It is even higher among those with histories of injecting drug use. As part of the state's strategy to minimise the spread of blood borne viruses and promote healthy lifestyles among prisoners, the Community Restorative Centre broadcasts a weekly half hour radio programme to prisoners and the community. The project is funded through the NSW Health Department and aims to provide support to prisoners, ex-prisoners and their families. Jailbreak's success hinges on the participation of the very people [prisoners] the show wishes to target. The radio show is aimed specifically at broadcasting health promotion and harm-minimisation messages to prisoners and their supporters although this is not obvious. When you tune in to Jailbreak you will hear a diverse range of opinion, music and poetry from people caught up in the criminal justice system. Nevertheless at the heart of this exciting and challenging project is the delivery of engaging, relevant and clear health messages to prison inmates, ex-inmates and families in relation to HIV, hepatitis and sexual health. Since 2002, valuable health information, often in the form of personal stories, vignettes and quiz questions, can be heard in and around Sydney on 2SER 107.3 FM or online at http://www.2ser.com. Jailbreak has not been without controversy and has to balance the security focus of correctional authorities and the illegality of substance use in correctional centres with the need to convey messages to prisoners in relation to harm-minimisation.     

The neutral zone impression revisited

The neutral zone technique is an alternative approach for the construction of lower complete dentures. It is most effective for dentures where there is a highly atrophic ridge and a history of denture instability. The technique aims to construct a denture that is shaped by muscle function and is in harmony with the surrounding oral structures. The technique is by no means new but is a valuable one. This paper aims to provide clinicians with the knowledge to use the technique - a list of competencies is included.     

Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder

BACKGROUND: Obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia. METHOD: This 14-week, multicenter, open-label, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight. RESULTS: Seventy-two patients were enrolled. The mean +/- SD weight loss at endpoint was significant in both groups (p < .05) and numerically greater in patients receiving BT than in those receiving UC (-2.0 +/- 3.79 and -1.1 +/- 3.11 kg, respectively). More patients in the BT group than in the UC group had lost > or = 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (complete population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027). CONCLUSION: BT may be an effective method for weight reduction in patients with chronic psychotic illness.