Health Literacy, Self-Efficacy and Glycemic Control in Patients With Diabetes Type 2 in a Greek Population.

Aim  To investigate the relationship between health literacy (HL), self-efficacy (SE), and achievement of treatment goals in patients with type 2 diabetes mellitus (T2DM). Method The cross-sectional study was conducted with a random sample of patients with T2DM attending the diabetology clinic and the Home Care department of the General Hospital of Drama, Greece. They completed two questionnaires: the short form of the European Health Literacy Survey Questionnaire (HLS-EU-Q16) to measure HL and the Diabetes Management Self-Efficacy Scale (DMSES) for people with T2DM to measure SE. Medical history, demographic characteristics, and values related to glycemic control were also recorded. Linear regression analysis was used to search for the dependence of glycosylated hemoglobin (A1C) values with HL and SE and the dependence between them. Result About 120 patients with T2DM (response rate of 92.3%) were enrolled in the study. The mean age of the participants was 62.5 years [standard deviation (SD) = 10.6 years] and most of them were female (53.3%). A1C was found to be significantly negatively associated with diet, physical activity, and SE score. Also, a statistically significant positive correlation was found between HL and SE. HL was correlated with age, gender, education level, and A1C, with women and older people having lower HL, while conversely higher education level was significantly associated with higher HL. Higher A1C was significantly associated with lower HL. Also, SE partially mediates the relationship between HL and A1C, in a significant way. Conclusion The results of the study confirm the important role of HL and SE in the successful management of T2DM. Multi-level educational interventions for diabetic patients could improve HL and SE and promote diabetes self-management.

Real-world effectiveness of vortioxetine in outpatients with major depressive disorder: functioning and dose effects.

BACKGROUND: Functional recovery is an important treatment goal in major depressive disorder (MDD). This study assessed the real-world effectiveness of vortioxetine in patients with MDD, with particular focus on functioning; dose-response was also assessed. METHODS: This was a non-interventional, prospective, multicenter study conducted in Greece. Adult outpatients with MDD (n = 336) initiating vortioxetine (5-20 mg/day flexible dosing) as treatment for a current major depressive episode were followed for 3 months. Analyses were stratified according to vortioxetine dosage at 3 months: 5-10 mg/day versus 15-20 mg/day. Functioning was assessed using the Sheehan Disability Scale (SDS). RESULTS: Mean ± standard error SDS total score decreased (improved) from 18.7 ± 0.3 at baseline to 12.9 ± 0.3 after 1 month of vortioxetine treatment and 7.8 ± 0.4 after 3 months (p < 0.001 vs. baseline for all comparisons). Functional recovery (SDS score ≤ 6) was achieved in 14.6% of patients after 1 month of treatment and 48.4% of patients after 3 months. Improvement from baseline in SDS total and domain scores at 3 months was more pronounced in patients receiving vortioxetine 15-20 mg/day than in those receiving vortioxetine 5-10 mg/day. The mean ± standard error change in SDS total score from baseline was 9.2 ± 0.8 in the 5-10 mg/day group and 12.1 ± 0.4 in the 15-20 mg/day group (p < 0.001). Limitations of this study include its non-interventional study design and lack of a control group or active comparator. CONCLUSIONS: Statistically significant and clinically relevant improvements in functioning were seen in patients with MDD treated with vortioxetine in a real-world setting. Higher doses of vortioxetine were associated with significantly greater improvements in functioning.

Paternal age and specific neurological soft signs as reliable and valid neurobiological markers for the diagnosis of patients with schizophrenia.

Advanced parental age at delivery and neurological soft signs (NSS) constitute risk factors for schizophrenia. The aim of the current study was to develop a neurobiological diagnostic index by combining them, and without the contribution of clinical symptomatology. The study sample included 133 patients suffering from schizophrenia according to DSM-IV-TR (77 males and 56 females; aged 33.55 ± 11.22 years old) and 122 normal controls (66 males and 56 females; aged 32.89 ± 9.91 years old). The assessment included the Neurological Evaluation Scale (NES), and a number of scales assessing the clinical symptoms and adverse effects. The statistical analysis included exploratory t-test, Pearson Correlation coefficient (R) and Discriminant Function Analysis (DFA). Exploratory t-tests and Pearson's R suggested that sex, parental age and NSS constitute independent components. On the basis of DFA results, the Psychotic Neurological Index was developed. At the cut-off PNI score of 8.5, sensitivity was equal to 94.74 and specificity to 93.44. The current is probably the first study to report on an easily obtainable diagnostic neurobiological marker with identifiable properties which is absolutely independent from the clinical manifestations and could serve in distinguishing between patients with schizophrenia and healthy controls with high efficacy.

Chronic myelogenous leukemia occurring in two brothers: The opposite sides of the same coin?

Herein we present a rare case of two brothers diagnosed with CML four years apart. Importantly, our case of CML occurrence among siblings is the fifth one reported and the second one investigated by both, conventional cytogenetics and RT-PCR analysis. Moreover, although Ph chromosome was detected in both our patients, RT-PCR revealed the presence of two different BCR-ABL transcripts. Finally, both our patients have been followed for a long period of time offering thus the opportunity to observe the differences in the clinical course.

Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1.

Next generation sequencing studies in Chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. Therefore, we assessed their incidences and associations with other clinical and genetic markers in the prospective multicenter COMPLEMENT1 trial (treatment naive patients not eligible for intensive treatment randomized to chlorambucil (CHL) vs. ofatumumab-CHL (O-CHL)). Baseline samples were available from 383 patients (85.6%) representative of the total trial cohort. Mutations were analyzed by amplicon-based targeted next generation sequencing (tNGS). In 52.2% of patients we found at least one mutation and the incidence was highest in NOTCH1 (17.0%), followed by SF3B1 (14.1%), ATM (11.7%), TP53 (10.2%), POT1 (7.0%), RPS15 (4.4%), FBXW7 (3.4%), MYD88 (2.6%) and BIRC3 (2.3%). While most mutations lacked prognostic significance, TP53 (HR2.02,p<0.01), SF3B1 (HR1.66,p=0.01) and NOTCH1 (HR1.39,p=0.03) were associated with inferior PFS in univariate analysis. Multivariate analysis confirmed the independent prognostic role of TP53 for PFS (HR1.71,p=0.04) and OS (HR2.78,p=0.02) and of SF3B1 for PFS only (HR1.52,p=0.02). Notably, NOTCH1 mutation status separates patients with a strong and a weak benefit from ofatumumab addition to CHL (NOTCH1wt:HR0.50,p<0.01, NOTCH1mut:HR0.81,p=0.45). In summary, TP53 and SF3B1 were confirmed as independent prognostic and NOTCH1 as a predictive factor for reduced ofatumumab efficacy in a randomized chemo (immune)therapy CLL trial. These results validate NGS-based mutation analysis in a multicenter trial and provide a basis for expanding molecular testing in the prognostic workup of patients with CLL. ClinicalTrials.gov registration number: NCT00748189.

One-year Outcome of First vs. Later Episode Schizophrenia: A Real-world Naturalistic Study.

OBJECTIVE: The aim the study was to calculate remission, recovery and relapse rates in first episode patients with schizophrenia (FES) vs. patients at a later phase (non-FES). METHODS: Thirty-two FES and 101 non-FES patients took part in the study. The assessment included testing at baseline and at 1 year with the Positive and Negative Syndrome Scale (PANSS), Calgary Depression scale, State-Trait Anxiety Inventory (STAI), Udvalg for Kliniske Undersøgelser (UKU) scale, Simpson Angus, and General Assessment of Functioning (GAF) subscale. The statistical analysis included chi-square test and analysis of covariance. RESULTS: At baseline 15.62% FES vs. 10.89% non-FES patients were in remission; none of FES vs. 2.97% non-FES patients were in recovery. At endpoint, the respective figures were 12.50% vs. 25.00% and 3.12% vs. 3.96%. None of the differences in rates was significant between the two groups except from the percentage of patients being under medication (higher in the non-FES group). Baseline PANSS negative subscale (PANSS-N) was the only predictor of the outcome at endpoint. CONCLUSION: The current study reported very low rates of remission and recovery of patients with schizophrenia without any differences between FES and non-FES patients. One possibility is that the increased antipsychotic treatment compensates for the worsening of the illness with time. An accumulating beneficial effect of antipsychotic treatment suggested that early lack of remission is not prognostic of a poor outcome.

A five-year follow-up of untreated patients with chronic lymphocytic leukaemia treated with ofatumumab and chlorambucil: final analysis of the Complement 1 phase 3 trial.

The Complement 1 trial investigated the efficacy and safety of ofatumumab + chlorambucil with chlorambucil monotherapy in patients with previously untreated chronic lymphocytic leukaemia (CLL). On long-term follow-up in the chemoimmunotherapy arm vs. the chemotherapy arm there was an estimated 12% (not significant) and 39% risk reduction in overall survival and progression-free survival, respectively. A high rate (61%) of treatment with next-line therapies in both the treatment arms may dilute any potential OS difference and confound the interpretation of the OS results. Addition of ofatumumab to chlorambucil demonstrated clinical benefit and tolerability as a frontline treatment option in patients unfit for fludarabine-containing therapy, with no new safety concerns.

The effect of baseline antipsychotic status on the 12-month outcome in initially stabilized patients with schizophrenia.

INTRODUCTION: Recently, the usefulness of antipsychotics has been challenged. The aim of the study was to measure the real-life effect of antipsychotic treatment on remission and recovery rates in already stabilized patients with schizophrenia after 1 year. MATERIAL AND METHODS: The study included 133 stabilized patients with schizophrenia (77 males and 56 females; aged 33.55 ± 11.22 years). The assessment included testing at baseline and after 1 year with the Positive and Negative Syndrome Scale, Calgary Depression Scale, State-Trait Anxiety Inventory, UKU, Extrapyramidal Symptom Rating Scale, and General Assessment of Functioning. RESULTS: More patients were on antipsychotics after 1 year (increase by 16.45%). There was an increase in the remission by 75% and in the recovery rate by 66%. It was not possible to predict the outcome on the basis of baseline variables. DISCUSSION: There is an accumulating beneficial effect of antipsychotic treatment over a 12-month period; early lack of remission is not prognostic of a poor outcome. There might be different neurobiological mechanisms underlying acute and sustained response. Both remission and recovery are difficult to achieve for patients with schizophrenia and characterize only a minority of patients. Only a very small minority of patients (4.5%) that is impossible to identify a priori would do well without off antipsychotics.

12-Month stability of neurological soft signs in stabilized patients with schizophrenia.

Objective: Neurological soft signs (NSS) are a group of minor non-localizable neurological abnormalities found more often in patients with schizophrenia. The aim of the current study was to investigate their temporal stability and relationship to the overall outcome over a 12-month period. Material and methods: The study sample included 133 stabilized patients suffering from schizophrenia (77 males and 56 females; aged 33.55 ± 11.22 years old). The assessment included the application at baseline and after 12 months of the Neurological Evaluation Scale (NES), and a number of scales assessing the clinical symptoms and adverse effects. The statistical analysis included ANOVA, exploratory t-test and Pearson correlation coefficients with Bonferroni correction. Results: In stabilized patients, NSS are stable over a 12-month period with only the subscale of NES-sensory integration manifesting a significant worsening, while, in contrast, most of the clinical variables improved significantly. There was no relationship of NES scores with the magnitude of improvement. The only significant negative correlation was between NES-motor coordination and Positive and Negative Syndrome Scale-GP change at 1 year. Discussion: The results of the current study suggest that after stabilization of patients with schizophrenia, there are probably two separate components, a 'trait' which is stable over a 12-month period, and a 'degenerative' component with a tendency to worsen probably in parallel with the progression of the illness and in correlation with the worsening of negative symptoms. However, the statistical support of the 'degenerative' component is weak. Significant outcomes Neurological softs signs are stable over a 12-month period, with the exception of 'sensory integration' which manifests significant improvement irrespective of treatment response. They do not respond to treatment with antipsychotics. They do not constitute a prognostic factor to predict improvement over a period of 1 year. Neurological soft signs constitute a trait symptom of schizophrenia which is stable though time. Limitations All the subjects have been previously hospitalized which may represent a more severe form of schizophrenia. Also, all patients were under antipsychotic and some also under benzodiazepine medications. Patients with comorbid somatic disorders were excluded which may decrease generalizability of results.

A case-control study of paternal and maternal age as risk factors in mood disorders.

Objective: Advanced parental age might constitute a risk factor for various disorders. We tested whether this concerns also mood disorder patients. Methods: The study included 314 subjects (42 bipolar-BD patients; 21 manics and 21 depressives, 68 unipolar-UD, and 204 normal controls-NC). Analysis of Covariance (ANCOVA) and the calculation of the Relative Risk (RR) and the Odds Ratio (OR) were used for the analysis. Results: Paternal age differed between NC and UD patients (29.42 ± 6.07 vs. 32.12 ± 5.54; p = .01) and manics (29.42 ± 6.07 vs. 35.00 ± 5.75; p = .001) and maternal age between NC and manics (25.46 ± 4.52 vs. 31.43 ± 4.75; p < .001) and manic and UD (31.43 ± 4.75 vs. 26.75 ± 6.03; p = .002). The RR and OR values suggested that advanced parental age constitutes a risk factor for the development of mood disorders. Conclusions: In a non-dose dependent and gender-independent, advanced parental age constitutes a risk factor for the development of BD with index episode of mania (probably manic predominant polarity); only advanced paternal age constitutes a risk factor for the development of UD and BD with index episode of depression (probably depressive predominant polarity). This is the first study suggesting differential effect of advanced parental age depending on predominant polarity of BD.

Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations.

The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Neurological soft signs in familial and sporadic schizophrenia.

OBJECTIVE: Neurological soft signs (NSS) are a group of minor non-localizable neurological abnormalities found more often in patients with schizophrenia. The aim of the current study was investigate whether there is any difference in their manifestation in familial vs. sporadic schizophrenia. MATERIAL AND METHODS: The study sample included 120 patients suffering from schizophrenia according to DSM-5 (71 males and 49 females; aged 32.79 ±â€¯11.11 years old) and 110 normal controls (57 males and 53 females; aged 33.38 ±â€¯10.14 years old). The assessment included the Neurological Evaluation Scale (NES) and the detailed investigation family history. The statistical analysis included exploratory Analysis of Covariance. RESULTS: The results of the current study suggest that NSS are more frequent in familial cases of schizophrenia and are even more pronounced in cases with family history of psychosis in either first or second degree relatives. DISCUSSION: Overall the results suggest the presence of a spectrum of increasing severity from healthy controls to sporadic cases, to cases with non-psychotic family history and eventually to cases with psychotic family history, rather than a categorical distribution.

Prevalence and correlates of neurological soft signs in healthy controls without family history of any mental disorder: A neurodevelopmental variation rather than a specific risk factor?

OBJECTIVE: Neurological soft signs (NSS) are a group of minor non-localizable neurological abnormalities found more often in patients with schizophrenia and other mental disorders. The aim of the current study was to investigate their prevalence and correlates in healthy controls without family history of any mental disorder. MATERIAL AND METHODS: The study sample included 122 normal subjects (66 males and 56 females; aged 32.89 ±â€¯9.91 years old). The assessment included the Neurological Evaluation Scale (NES), and a number of scales assessing the subthreshold symptoms (MADRS, STAI) and functioning (GAF). Data on a number of socio-demographic variables were also gathered. The statistical analysis included the development of basic statistics tables and the calculation of Pearson correlation coefficients. RESULTS: The results of the current study suggest that more than half of the study sample manifested at least one NSS and approximately 5% more than four. Still, the reported prevalence and NES scores are lower form those reported in the literature probably because of the carefully selected study sample. There were no significant correlations between NSS and any socio-demographic or clinical variable. DISCUSSION: The current study is the first to study NSS in subjects without family history of any mental disorder and reports the presence of frequent silent neurodevelopmental events in the general population, probably in the form of a neurodevelopmental variation and possibly a weak generic rather than specific risk factor.

Paternal and maternal age as risk factors for schizophrenia: a case-control study.

OBJECTIVE: Advanced parental age might constitute a generic risk factor for mental and somatic disorders. The current study tested whether this concerns also patients with schizophrenia. METHODS: A total of 231 schizophrenic, 56 other severe mental disorders patients and 204 controls were diagnosed according to DSM-IV-TR. Data were tested with ANOVA models including relative risk and odds ratios. RESULTS: Patients with schizophrenia manifested higher paternal (32.55 ± 6.35 vs. 29.42 ± 6.07, p < .001) and maternal age (27.66 ± 5.57 vs. 25.46 ± 4.52, p < .001). Patients with other mental disorders had higher paternal (33.29 ± 8.35; p = .001) but not maternal age (26.69 ± 5.89; p = .296) compared to controls. There was no difference between the two patient groups concerning either paternal or maternal age (p > .05). There seems to be a higher risk for the development of schizophrenia in offspring with paternal age above 25 years and maternal age above 22 years at delivery. CONCLUSIONS: The current study provides further support for the suggestion that advanced paternal age constitutes a risk factor (in a non-dose dependent and gender-independent way) for the development of schizophrenia but also for other mental disorders. In contrast, advanced maternal age characterises schizophrenia specifically. The higher risk is evident after 25 years of paternal and 22 years of maternal age, respectively.

Labile plasma iron levels predict survival in patients with lower-risk myelodysplastic syndromes.

Red blood cell transfusions remain one of the cornerstones in supportive care of lower-risk patients with myelodysplastic syndromes. We hypothesized that patients develop oxidant-mediated tissue injury through the formation of toxic iron species, caused either by red blood cell transfusions or by ineffective erythropoiesis. We analyzed serum samples from 100 lower-risk patients with myelodysplastic syndromes at six-month intervals for transferrin saturation, hepcidin-25, growth differentiation factor 15, soluble transferrin receptor, non-transferrin bound iron and labile plasma iron in order to evaluate temporal changes in iron metabolism and the presence of potentially toxic iron species and their impact on survival. Hepcidin levels were low in 34 patients with ringed sideroblasts compared to 66 patients without. Increases of hepcidin and non-transferrin bound iron levels were visible early in follow-up of all transfusion-dependent patient groups. Hepcidin levels significantly decreased over time in transfusion-independent patients with ringed sideroblasts. Increased soluble transferrin receptor levels in transfusion-independent patients with ringed sideroblasts confirmed the presence of ineffective erythropoiesis and suppression of hepcidin production in these patients. Detectable labile plasma iron levels in combination with high transferrin saturation levels occurred almost exclusively in patients with ringed sideroblasts and all transfusion-dependent patient groups. Detectable labile plasma iron levels in transfusion-dependent patients without ringed sideroblasts were associated with decreased survival. In conclusion, toxic iron species occurred in all transfusion-dependent patients and in transfusion-independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion-dependent patients. clinicaltrials.gov Identifier: 00600860.