Oral and Palmitate Paliperidone Long-Acting Injectable Formulations' Use in Schizophrenia Spectrum Disorders: A Retrospective Cohort Study from the First Episode Psychosis Intervention Program (CRUPEP).

BACKGROUND: Long-acting injectable antipsychotics (LAIs) may be a suitable therapeutic option for those patients in earlier stages of psychosis to avoid relapses and disease progression. Despite that, there is a lack of evidence in the literature regarding the use of LAIs in this profile of patients. METHODS: This is a retrospective cohort analysis to assess the efficacy, tolerability, and pattern of use of palmitate paliperidone long-acting injectable (PPLAI) formulations (1- and 3-month doses) compared to oral paliperidone/risperidone in patients with a nonaffective first episode of psychosis (FEP) over 12 months of follow-up. Relevant sociodemographic and clinical information were assessed, as well as main clinical scales: Positive and Negative Syndrome Scale, Personal and Social Performance Scale, and Clinical Global Impression Scale Improvement and Severity measures. RESULTS: The study included 48 patients, 16 per arm, who were aged 20-50 years and had an FEP. Significant improvements were registered for all treatment groups. Despite that, patients receiving PPLAI 1- and 3-month formulations obtained greater improvements than those in the oral group in the main domains assessed (P < .001). We found no statistically significant differences in hospitalizations between groups. Side effects were presented in 24% of patients. A trend towards reducing antipsychotic doses was observed in 43.8% of patients to achieve the minimum effective dose and avoid the occurrence of side effects. CONCLUSIONS: To our knowledge, this is the first study assessing the use of palmitate paliperidone long-acting formulations versus oral risperidone or paliperidone in FEP. Treatment with PPLAI formulations seems to be an effective therapeutic choice at earlier stages of the disease.

Influence of social cognition as a mediator between cognitive reserve and psychosocial functioning in patients with first episode psychosis.

BACKGROUND: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. METHODS: The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. RESULTS: At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). CONCLUSIONS: Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

Lung deposition of aclidinium bromide from Genuair, a multidose dry powder inhaler.

BACKGROUND: Aclidinium bromide is a novel, long-acting inhaled muscarinic antagonist currently in development for the treatment of chronic obstructive pulmonary disease (COPD). A next-generation multidose dry powder inhaler will be used for the delivery of aclidinium bromide. OBJECTIVES: To quantify whole lung deposition and regional lung deposition of aclidinium delivered by a multidose dry powder inhaler (Genuair) in healthy subjects. METHODS: A single dose (200 microg) of aclidinium bromide, radiolabelled with (99m)Tc, was administered from the multidose dry powder inhaler at a targeted peak inspiratory flow rate (PIFR) of 90 litres/min in 12 healthy males (18-63 years). Gamma scintigraphy was used to quantify drug deposition in the lungs and oropharynx, as well as amounts retained in the inhaler and exhaled. The quantities of drug deposited in 6 concentric regions within the lungs were also determined. RESULTS: The mean (+/- SD) PIFR was 79.0 +/- 9.4 litres/min. The mean (+/- SD) percentages of the metered dose deposited in the whole lung and oropharynx were 30.1 +/- 7.3 and 54.7 +/- 7.2%, respectively. Deposition of aclidinium occurred in all 6 lung zones, but was highest in the most central zone. CONCLUSIONS: These results demonstrated that the multidose dry powder inhaler delivered aclidinium efficiently to the lungs. The whole lung deposition seen in this study is an indication of the likely whole lung deposition in COPD patients who inhale with similar PIFRs; however, further studies in patients are required to confirm this.

PCR amplification of streptococcal DNA using crude cell lysates.

Gram-positive organisms such as streptococci and enterococci are often difficult to lyse. Obtaining DNA for procedures such as PCR amplification usually requires a large scale isolation for each strain under investigation. We describe a simple procedure for small volumes of whole cells, involving pretreatment with detergent and proteinase that allows for efficient release of DNA for PCR amplification. This procedure is fast, reproducible, can be used with a large number of samples, and has been successfully applied to a variety of streptococcal and enterococcal strains.

Longitudinal changes of insight in first episode psychosis and its relation to clinical symptoms, treatment adherence and global functioning: one-year follow-up from the Eiffel study.

OBJECTIVES: The Eiffel study is a longitudinal, naturalistic study of patients with first episode psychosis (FEP) designed to evaluate the predictive value of defective insight on treatment adherence and global functioning. METHODS: Five hundred seventy-seven patients with FEP were assessed at baseline and at a 1-year follow-up. They were compared in terms of sociodemographic factors, psychopathology, insight, treatment adherence and functional outcome. Longitudinal functionality was prospectively assessed with the clinical global impression (CGI) and global assessment of functioning (GAF) rating scales. RESULTS: At baseline, up to 50% of our sample presented with a lack of insight. Most clinical symptoms, including insight, improved over the follow-up period. Insight, education and social withdrawal significantly predicted CGI and GAF at follow-up. Insight and level of education were predictive of treatment adherence. CONCLUSIONS: Insight significantly predicted the general clinical course, treatment adherence and functional outcome in our FEP sample after 1 year. Only education additionally accounted for the longitudinal course. Since our results suggest that better insight improves treatment adherence and consequently clinical course and functional outcome, insight could be a specific target of treatment in early intervention programs.

Dispositivo intrauterino migrado a la cavidad abdominal con embarazo intrauterino no evolutivo: reporte de caso / Intrauterine device migrated to the abdominal cavity with non-progressive intrauterine pregnancy: case report

La migración de un dispositivo intrauterino a la cavidad abdominal es una complicación poco frecuente de este eficaz método contraceptivo, sin embargo debe sospecharse ante la imposibilidad de visualizar los hilos del dispositivo vía vaginal y la ausencia intrauterina del mismo por ecografía. Si bien la migración abdominal puede ser asintomática, algunos casos pueden producir clínica de severidad variable incluyendo dolor abdominal y complicaciones derivadas de la formación de adherencias o la perforación de vísceras pélvicas y abdominales. Su detección intraabdominal debe sospecharse en primer lugar por ecografía y confirmarse mediante radiología simple de abdomen. Una vez localizado el dispositivo migrado, se recomienda su extracción inmediata, incluso en casos asintomáticos, con el fin de evitar las complicaciones derivadas de su desplazamiento. La laparoscopia será de primera elección en estos casos para la extracción. Presentamos un caso de migración intraabdominal de dispositivo intrauterino concurrente a un embarazo intrauterino no evolutivo.

Migration of an intrauterine device to the abdominal cavity is a rare complication of this effective contraceptive method, however, it must be suspected upon the inability to visualize the wires vaginally and the absence of intrauterine device by ultrasound. While its abdominal migration can be asymptomatic, some cases may produce variable clinical severity including abdominal pain and complications resulting from the formation of adhesions or perforation of pelvic and abdominal viscera. Its intraabdominal detection should be suspected first by ultrasound and confirmed by plain abdominal X-ray. Once the migrated device is located, immediate removal is recommended, even in asymptomatic cases, in order to avoid complications arising from its displacement. Laparoscopy will be the first choice in these cases for extraction. We report a case of intraabdominal migration of intrauterine device concurrent with a non-evolutive intrauterine pregnancy.

[Duration of untreated psychosis as predictive and prognostic factor in the course of first episode psychosis]. / El tiempo de psicosis no tratada como factor predictivo y pronóstico en el curso de los primeros episodios psicóticos.

INTRODUCTION: Recently, many studies have focused on the duration of untreated psychosis (DUP) in order to clarify if DUP could be one of the factors that would influence prognosis of psychotic disease. MATERIAL AND METHODS: We present a one year follow - up study with 90 medication native, first episode psychotic patients. The likely prognosis factors that could influence in the outcome of the disease were measured. Therefore, we used a protocol including the following scales: PANSS, Psychosocial Stress Global Assessment scale (DSM IIIR), Global Assessment of Functioning scale (GAF-EEAG), Clinical Global Impression (CGI), Montgomery-Asberg scale for the depression, Young mania rating scale, abnormal involuntary movements scale, UKU scale for extrapyramidal symptoms and Premorbid Adjustment scale (Cannon-Spoor). Assessments were made every three months for 1 year. A statistical analysis of data was performed. RESULTS: As a result, it was concluded that there was no relationship between a long duration untreated psychosis and a worse outcome of the illness in our sample. The only related factors with the prognosis were premorbid adjustment and the type of disease onset. Hence, the patients with a better premorbid adjustment and an acute onset of psychosis had a better outcome. CONCLUSION: Our study represents more evidence in favor of the independence of DUP and disease outcome.

An HlyB-type function is required for expression of the Enterococcus faecalis hemolysin/bacteriocin.

The nucleotide sequence of a 3,422-bp internal restriction fragment from the Enterococcus faecalis pAD1 hemolysin/bacteriocin-encoding region was determined. This fragment was associated with expression of hemolysin/bacteriocin component L and contained a 2,142-bp open reading frame. The inferred amino acid sequence revealed a protein which shared extensive similarity with HlyB of the Escherichia coli alpha-hemolysin operon. The inferred protein, CylB, was observed to be independently expressed in E. coli and capable of complementing an insertion mutation in the cloned hemolysin/bacteriocin operon in trans. Despite the extensive similarity to HlyB, CylB was incapable of complementing an insertion mutation in hlyB. Cytolysin determinants possessing an HlyB-type transport function are widely dispersed throughout gram-negative genera. We believe this to be the first example of an HlyB-type protein encoded within a cytolysin determinant from a gram-positive bacterium.

[Design and validation of a questionnaire in Spanish for measuring the quality of life in postmenopausal women: the MENCAV questionnaire]. / Diseño y validación de un cuestionario en castellano para medir calidad de vida en mujeres posmenopáusicas: el cuestionario MENCAV.

OBJECTIVE: To calculate the validity and reliability of a questionnaire to measure the quality of life in post-menopausal women. DESIGN: Cross-sectional observation study. SETTING: Three health districts in the province of Cuenca. PARTICIPANTS: 203 menopausal women between 44 and 60 years of age, chosen through simple randomised sampling. MEASUREMENTS AND MAIN RESULTS: On the basis of the analysis of various scales of health-related quality of life, some for measuring physical disorders, and others for psychological disorders, a questionnaire was designed. This had 85 items structured as a Likert-like additive scale and explored four dimensions (physical health, psychological health, family environment and social support). In the view of a multi-disciplinary group of health professionals, it met criteria of logical validity and validity of contents for the different spheres that are usually affected in the menopause. After the administration of the questionnaire to the women taking part, a process of "purging" items began, in which those items with a reply frequency to one of the five options of below 5% or above 95% were discarded. Also discarded were those items for which the inter-item correlation was below 0.20, with analysis too of the behaviour of the Cronbach's alpha coefficient as each item was eliminated from its scale. Finally, through exploratory factorial analysis techniques (main components), the distribution of the items in dimensions was evaluated. A final questionnaire made up of 37 items in 5 dimensions, which we named physical health, psychological health, family environment, sexual relationships and social support was reached. This questionnaire had an overall Cronbach's alpha value of 0.84. Finally, the correlations existing between the sum of scores of the items on each of the dimensions were analysed. The correlation coefficients showed values between 0.08 and 0.69. CONCLUSIONS: The MENCAV questionnaire is the first in Spanish which assesses quality of life in menopausal women. Experts analysed its logical validity and contents validity and found it had a high degree of internal consistency.

Genetic analysis of the pAD1 hemolysin/bacteriocin determinant in Enterococcus faecalis: Tn917 insertional mutagenesis and cloning.

Thirty-seven nonhemolytic/nonbacteriocinogenic mutations in Enterococcus (Streptococcus) faecalis plasmid pAD1 were generated by Tn917 insertion. All were found to belong to one of two complementation classes. Each class of mutants secreted either hemolysin/bacteriocin (Hly/Bac) component A or L into the culture medium. DNA encoding Hly/Bac was cloned in Escherichia coli in which both components of the hemolysin were expressed individually and collectively. The region encoding components A and L was further defined by deletion analysis and physically mapped. A total of approximately 8.4 kilobases of pAD1 DNA were observed to be required for hemolysin expression. Hly/Bac activity of the wild-type and the inactive L substance was observed to be heat stable. Active Hly/Bac resulting from incubating separately secreted components A and L was also found to be heat stable. The results indicate that component A activates component L and that activated component L possesses the Hly/Bac activity. Component A was also observed to be associated with host immunity to the Hly/Bac.

Genetic structure of the Enterococcus faecalis plasmid pAD1-encoded cytolytic toxin system and its relationship to lantibiotic determinants.

Pheromone-responsive conjugative plasmids are unique to the species Enterococcus faecalis. Many pheromone-responsive plasmids, including those frequently isolated from sites of infection, express a novel cytolysin that possesses both hemolytic and bacteriocin activities. Further, this cytolysin has been shown to be a toxin in several disease models. In the present study, nucleotide sequence determination, mutagenesis, and complementation analysis were used to determine the organization of the E. faecalis plasmid pAD1 cytolysin determinant. Four open reading frames are required for expression of the cytolysin precursor (cylLL, cylLS, cylM, and cylB). The inferred products of two of these open reading frames, CyILL and CyILS, constitute the cytolysin precursor and bear structural resemblance to posttranslationally modified bacteriocins termed lantibiotics. Similarities between the organization of the E. faecalis cytolysin determinant and expression units for lantibiotics exist, indicating that the E. faecalis cytolysin represents a new branch of this class and is the first known to possess toxin activity.

Molecular characterization of the Enterococcus faecalis cytolysin activator.

The gene encoding component A (cylA), the activator protein of the Enterococcus faecalis cytolysin, has been localized on pAD1, and the nucleotide sequence was determined. cylA consists of a 1,236-bp open reading frame encoding a 412-amino-acid polypeptide. A search of the National Biomedical Research Foundation data base revealed significant homology between the inferred amino acid sequence of component A and subtilisin BPN'. Component A activation of the cytolysin precursor (component L) was observed to be inhibited by the serine protease inhibitor diisopropylfluorophosphate. Mature component A exhibits a molecular weight of approximately 30,000 and an isoelectric point of 4.5. Differences between the size of the primary translation product (45,625 daltons) and the mature enzyme suggest that, as for subtilisin, component A is secreted as a proenzyme. These results provide the basis for a model of component A activation of component L and a role for component A in protecting the cytolysin-producing cell from lysis.

Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study.

In this double-blind study, the efficacy and tolerability of a single dose of almotriptan (6.25 or 12.5 mg) was compared with placebo in the treatment of three consecutive migraine attacks of moderate or severe intensity. Of 1013 randomized patients, 722 evaluable patients completed the study. The total number of attacks relieved (severe or moderate pain reduced to mild or no pain) at 2 h post-dose was significantly higher (P < 0.001) after treatment with almotriptan 6.25 or 12.5 mg compared with placebo (60% and 70% vs. 38%, respectively). Moreover, a consistent response was achieved across and within patients for almotriptan 6.25 or 12.5 mg compared with placebo (pain relief in at least two out of three attacks within 2 h for 64% and 75% vs. 36%, respectively) and less than one-third of the patients relapsed within 24 h. Almotriptan was well tolerated with no significant differences between the almotriptan and placebo treatment groups in the percentage of patients reporting adverse events. Overall, the 12.5-mg dose was associated with the most favourable efficacy/tolerability ratio and is, therefore, the recommended dose.