Transcriptome Analysis of Pterygium and Pinguecula Reveals Evidence of Genomic Instability Associated with Chronic Inflammation.

Solar damage due to ultraviolet radiation (UVR) is implicated in the development of two proliferative lesions of the ocular surface: pterygium and pinguecula. Pterygium and pinguecula specimens were collected, along with adjacent healthy conjunctiva specimens. RNA was extracted and sequenced. Pairwise comparisons were made of differentially expressed genes (DEGs). Computational methods were used for analysis. Transcripts from 18,630 genes were identified. Comparison of two subgroups of pterygium specimens uncovered evidence of genomic instability associated with inflammation and the immune response; these changes were also observed in pinguecula, but to a lesser extent. Among the top DEGs were four genes encoding tumor suppressors that were downregulated in pterygium: C10orf90, RARRES1, DMBT1 and SCGB3A1; C10orf90 and RARRES1 were also downregulated in pinguecula. Ingenuity Pathway Analysis overwhelmingly linked DEGs to cancer for both lesions; however, both lesions are clearly still benign, as evidenced by the expression of other genes indicating their well-differentiated and non-invasive character. Pathways for epithelial cell proliferation were identified that distinguish the two lesions, as well as genes encoding specific pathway components. Upregulated DEGs common to both lesions, including KRT9 and TRPV3, provide a further insight into pathophysiology. Our findings suggest that pterygium and pinguecula, while benign lesions, are both on the pathological pathway towards neoplastic transformation.

Hospital stay in patients admitted for acute bipolar manic episodes prescribed quetiapine immediate or extended release: a retrospective non-interventional cohort study (HOME).

BACKGROUND: Bipolar manic episodes often require hospital admission to ensure patient safety. The antipsychotic quetiapine is a common treatment for bipolar mania and is available in immediate release (IR) and extended release (XR) formulations; however, outcomes in patients receiving these different formulations have not been directly compared in an acute hospital setting. METHODS: We conducted a multinational, observational, retrospective cohort study to describe and compare hospital stay in patients admitted for an acute bipolar manic episode treated with quetiapine IR or XR from 1 October 2009-1 October 2010. The primary outcome measure was comparison of length of stay (LOS) using zero-truncated negative binomial regression. RESULTS: In total, 1230 patients were included (659 in the IR cohort; 571 in the XR cohort). The median LOS (interquartile range) was 18.0 days (12.0, 28.0) in the IR cohort and 20.0 days (12.0, 34.0) in the XR cohort, respectively. LOS was not significantly associated with quetiapine formulation irrespective of whether or not clinical characteristics were taken into account (p = 0.820 and p = 0.386, respectively). Overall, 84.2% and 84.4% of patients in the IR and XR cohorts, respectively, had not previously used quetiapine; of these patients, 78.7% and 68.9% received one total daily dose, and 14.4% and 23.9% received dose titration. Over half of patients received antipsychotic monotherapy (53.1% and 58.3% in the IR and XR cohorts, respectively) and most received a daily quetiapine dose ≥ 400 mg (64.9% and 71.8%, respectively, for quetiapine monotherapy and 59.9% and 80.3%, respectively, for combination treatment). As a secondary outcome, multivariate analysis was used to identify other factors that affect LOS. Factors associated with a longer hospital stay included public funding versus private, maximum number of new medications administered, did not receive lithium and did not receive anxiolytics, sedatives/hypnotics (all p < 0.0001). Factors associated with a shorter hospital stay included presence of drug/alcohol abuse, living accompanied and having a psychiatric medical history (all p < 0.05). CONCLUSIONS: LOS was not found to be associated with quetiapine formulation. However, most patients received only one total daily dose of quetiapine without dose titration, which was unexpected and contrary to current recommendations. TRIAL REGISTRATION: NCT01239589.

Clinical management and burden of bipolar disorder: results from a multinational longitudinal study (WAVE-bd).

Bipolar disorder is a mood disorder which requires complex treatment. Current treatment guidelines are based on the results of published randomized clinical trials and meta-analyses which may not accurately reflect everyday clinical practice. This multi-national, multi-centre, observational cohort study describes clinical management and clinical outcomes related to bipolar disorder in real-life settings, assesses between-country variability and identifies factors associated with clinical outcomes. Adults from 10 countries in Europe and South America who experienced at least one mood episode in the preceding 12 months were included. Overall, 2896 patients were included in the analyses and followed for at least 9 months across a retrospective and prospective study phase. Main outcome measures were the number and incidence rate of mood episodes (relapses and recurrences) and healthcare resource use including pharmacological treatments. Relapses and recurrences were reported in 18.2 and 40.5% of patients, respectively; however, the reported incidence rate of relapses was higher than that of recurrences [1.562 per person-year (95% CI 1.465-1.664) vs. 0.691 per person-year (95% CI 0.657-0.726)]. Medication use was high during all episode types and euthymia; the percentage of patients receiving no medication ranged from 11.0% in mania to 6.1% in euthymia. Antipsychotics were the most commonly prescribed drug class in all disease phases except for patients with depression, where antidepressants were more frequently prescribed. Visits to the psychiatrist were the most frequently used healthcare resource. These results provide a description of treatment patterns for bipolar disorder across different countries and indicate factors related to relapse and recurrence.

Adaptation into Spanish of the Clinically Useful Depression Outcome Scale (CUDOS) for assessing major depressive disorder from the patient's perspective.

OBJECTIVE: To adapt the CUDOS scale (Clinically Useful Depression Outcome Scale) into Spanish and to test its psychometrical properties in a sample of patients with major depressive disorder (MDD). METHODS: A two-step cross-sectional, multicenter validation study was conducted (linguistic adaptation into Spanish and psychometric validation). The study evaluated patients attended in Primary Care with a MDD diagnosis within the last 3 months (DSM-IV TR criteria). The following scales were administered: CUDOS, PRIME-MD (Primary Care Evaluation of Mental Disorders), HAMD-17 (Hamilton Depression Rating Scale), SOFAS (Social and Occupational Functioning Assessment Scale), SF-36 (Physical ­PCS- and Mental ­MCS- Component Summaries), and the CGI-S & PGI-S (Clinical Global Impression for Severity of Illness scales for clinicians and patients, respectively). Feasibility, reliability, and validity of the Spanish version were assessed. RESULTS: In the validation study, 305 MDD patients (69.5% female) with a mean age (standard deviation-SD-) of 51.75(15.53) were included. Mean completion time was 4.47(2.4) minutes. Floor or ceiling effects were found in less than 1% of the case scores. Internal consistency was adequate (Cronbach's α= 0.88). Pearson correlation coefficients with CUDOS were: -0.42 (SOFAS), 0.45 (HAMD-17), -0.22 (PCS), -0.65 (MCS); all p<0.001. The CUDOS properly discriminated among clinical severity levels (p<0.03). CONCLUSIONS: The adapted Spanish version of the CUDOS shows adequate psychometric properties as an evaluation instrument of major depression from the patient's perspective.

Treatment patterns in major depressive disorder after an inadequate response to first-line antidepressant treatment.

BACKGROUND: The aim of the study was to determine the most common pharmacological strategies used in the management of major depressive disorder (MDD) after an inadequate response to first-line antidepressant treatment in clinical practice. METHODS: Multicenter, non-interventional study in adult outpatients with a DSM-IV-TR diagnosis of MDD and inadequate response to first-line antidepressant medication. Multiple logistic regression analyses were performed to identify independent factors associated with the adoption of a specific second-line strategy. RESULTS: A total of 273 patients were analyzed (mean age: 46.8 years, 67.8% female). Baseline mean Montgomery-Asberg Depression Rating Scale total score was 32.1 (95%CI 31.2-32.9). The most common strategies were: switching antidepressant medication (39.6%), augmentation (18.8%), and combination therapy (17.9%). Atypical antipsychotic drugs were the most commonly used agent for augmenting antidepressant effect. The presence of psychotic symptoms and the number of previous major depressive episodes were associated with the adoption of augmenting strategy (OR = 3.2 and 1.2, respectively). CONCLUSION: The switch to another antidepressant agent was the most common second-line therapeutic approach. Psychiatrists chose augmentation based on a worse patients' clinical profile (number of previous episodes and presence of psychotic symptoms).

Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd study).

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

Suboptimal treatment adherence in bipolar disorder: impact on clinical outcomes and functioning.

BACKGROUND: The primary aim of this study was to assess drug treatment adherence in patients with bipolar disorder and to identify factors associated with adherence. The secondary aim was to analyze the impact of suboptimal adherence on clinical and functional outcomes. METHODS: A cross-sectional study was conducted in a sample of outpatients receiving an oral antipsychotic drug. Medication adherence was assessed combining the 10-item Drug Attitude Inventory, the Morisky Green Adherence Questionnaire, and the Compliance Rating Scale. Logistic regression was used to determine significant variables associated with suboptimal adherence to medication. RESULTS: Three hundred and three patients were enrolled into the study. The mean age was 45.9 ± 12.8 years, and 59.7% were females. Sixty-nine percent of patients showed suboptimal adherence. Disease severity and functioning were significantly worse in the suboptimal group than in the adherent group. Multivariate analysis showed depressive polarity of the last acute episode, presence of subsyndromal symptoms, and substance abuse/dependence to be significantly associated with suboptimal treatment adherence (odds ratios 3.41, 2.13, and 1.95, respectively). CONCLUSION: A high prevalence of nonadherence was found in an outpatient sample with bipolar disorder. Identification of factors related to treatment adherence would give clinicians the opportunity to select more adequately patients who are eligible for potential adherence-focused interventions.

A short message service (SMS)-based strategy for enhancing adherence to antipsychotic medication in schizophrenia.

BACKGROUND: The aim of this study was to assess the impact of a short message service (SMS)-based strategy on adherence to antipsychotic treatment. METHODS: A multicentre, randomised, open-label, controlled, 6-month study with clinically stabilised outpatients with schizophrenia was conducted. The patients assigned to the intervention received daily SMS reminders to take their medication for 3 months. Self-reported medication adherence was determined using the Morisky Green Adherence Questionnaire (MAQ). Secondary outcomes were severity of illness, attitude towards medication, insight into illness and health-related quality of life. RESULTS: A total of 254 patients were analysed. A significantly greater improvement in adherence was observed among patients receiving SMS text messages compared with the control group. The mean change in MAQ total score from baseline to month 3 was -1.0 (95% confidence interval (CI) -1.02, -0.98) and -0.7 (95%CI -0.72, -0.68), respectively (P=0.02). Greater improvement in negative, cognitive and global clinical symptoms at month 3 was observed. Attitude towards medication also significantly improved across the study in the intervention group versus the controls. CONCLUSIONS: An SMS-based intervention seems feasible and acceptable for enhancing medication adherence. Further studies are needed to confirm whether this kind of intervention could be a complementary strategy to optimise adherence in schizophrenia.

Short-term clinical stability and lack of insight are associated with a negative attitude towards antipsychotic treatment at discharge in patients with schizophrenia and bipolar disorder.

PURPOSE: The primary aim of this study was to assess the range of attitudes towards antipsychotic treatment at hospital discharge in patients with schizophrenia and bipolar disorder. The secondary aim was to analyze the relationship between patients' attitudes and sociodemographic and clinical parameters. PATIENTS AND METHODS: A cross-sectional study with a sample of patients admitted due to acute exacerbation of schizophrenia or a manic episode was conducted. Attitude towards pharmacological treatment at discharge was assessed with the 10-item Drug Attitude Inventory (DAI-10). Logistic regression was used to determine significant variables associated with attitude to medication. RESULTS: Eighty-six patients were included in the study. The mean age was 43.1 years (standard deviation [SD] 12.1), and 55.8% were males. Twenty-six percent of the patients presented a negative attitude towards antipsychotic treatment (mean DAI-10 score of -4.7, SD 2.7). Most of them had a diagnosis of schizophrenia. Multivariate analysis showed that poor insight into illness and a greater number of previous acute episodes was significantly associated with a negative attitude towards medication at discharge (odds ratio 1.68 and 1.18, respectively). CONCLUSION: Insight and clinical stability prior to admission were related to patients' attitude towards antipsychotic treatment at hospital discharge among patients with schizophrenia and bipolar disorder. The identification of factors related to the attitude towards medication would offer an improved opportunity for clinicians to select patients eligible for prophylactic adherence-focused interventions.

Adaptación al castellano de la escala Clinically Useful Depression Outcome Scale (cudos) para la evaluación de la depresión mayor desde la perspectiva del paciente / Adaptation into spanish of the Clinically Useful Depression Outcome Scale (cudos) for assessing major depressive disorder from the patient’s perspective

Objetivo: Adaptar al castellano la escala CUDOS (Clinically Useful Depression Outcome Scale) y analizar sus propiedades psicométricas en pacientes con trastorno depresivo mayor (TDM).Método: Se realizó un estudio multicéntrico transversal de dos etapas (adaptación cultural y validación psicométrica) en el que se evaluaron pacientes en Atención Primaria con TDM diagnosticado (criterios DSM-IV TR) en los últimos3 meses. Junto a la escala CUDOS, se aplicaron los instrumentos: PRIME-MD (Primary Care Evaluation of Mental Disorders), HAMD-17 (Hamilton Depression Rating Scale), SOFAS (Social and Occupational Functioning Assessment Scale), SF-36 (Componentes Físico–PCS- y Mental–MCS-) y escalas CGI-SI y PGI-SI (Escala de Impresión Clínica Global de Gravedad según clínico o paciente, respectivamente).Se analizó la factibilidad, fiabilidad y validez de la versión adaptada. Resultados: En la fase de validación, se incluyeron 305pacientes (69,5% mujeres) con edad media (desviación típica)de 51,75(15,53) años. El tiempo medio de cumplimentación fue de 4,47(±2,4) minutos. Los efectos techo/suelo se encontraron en menos del 1% de los casos. La consistencia interna de la escala CUDOS fue adecuada (α de Cronbach=0,88). Los coeficientes de correlación de Pearson de CUDOS con otras escalas fueron: 0,42 (SOFAS); 0,45 (HAMD-17); -0,22 (PCS);-0,65 (MCS); p<0,001. La escala CUDOS discriminó adecuadamente entre los diferentes niveles clínicos de gravedad (p<0,03).Conclusiones: La versión adaptada de la escala CUDOS muestra propiedades psicométricas adecuadas como instrumento de evaluación de la depresión mayor desde la perspectiva del paciente (AU)

Objective: To adapt the CUDOS scale (Clinically Useful Depression Outcome Scale) into Spanish and to test its psychometrical properties in a sample of patients with major depressive disorder (MDD).Methods: A two-step cross-sectional, multicenter validation study was conducted (linguistic adaptation into Spanish and psychometric validation). The study evaluated patients attended in Primary Care with a MDD diagnosis within the last 3 months (DSM-IV TR criteria). The following scales were administered: CUDOS, PRIME-MD (Primary Care Evaluation of Mental Disorders), HAMD-17 (Hamilton Depression Rating Scale), SOFAS (Social and Occupational Functioning Assessment Scale), SF-36 (Physical –PCS- and Mental –MCS- Component Summaries), and the CGI-S &PGI-S (Clinical Global Impression for Severity of Illness scales for clinicians and patients, respectively). Feasibility, reliability, and validity of the Spanish version were assessed. Results: In the validation study, 305 MDD patients (69.5% female) with a mean age (standard deviation-SD-) of 51.75 (15.53) were included. Mean completion time was 4.47 (2.4) minutes. Floor or ceiling effects were found in less than 1% of the case scores. Internal consistency was adequate (Cronbach´s α= 0.88). Pearson correlation coefficients with CUDOS were: -0.42 (SOFAS), 0.45 (HAMD-17), -0.22 (PCS),-0.65 (MCS); all p<0.001. The CUDOS properly discriminated among clinical severity levels (p<0.03). Conclusions: The adapted Spanish version of the CUDOS shows adequate psychometric properties as an evaluation instrument of major depression from the patient’s perspective (AU)