Once Nocturia, Always Nocturia? Natural History of Nocturia in Older Men Based on Frequency-Volume Charts:The Krimpen Study

Purpose: Nocturia is a highly prevalent and bothersome symptom that might (spontaneously) resolve. However, longitudinal data are not available on the incidence and resolution of nocturia assessed with frequency-volume charts. In this study we determined the prevalence, incidence and resolution rates of nocturia assessed by frequency-volume charts, and compared nocturnal voiding frequency over time as assessed by frequency-volume charts and questionnaires. Materials and Methods: A longitudinal, population based study was conducted among 1,688 men 50 to 78 years old with followup rounds at 2.1, 4.2 and 6.5 years. Nocturnal voiding frequency was determined with frequency-volume charts and, for comparison purposes, with a question from the International Prostate Symptom Score. Nocturia was defined as nocturnal voiding frequency 2 or greater. Prevalence, incidence and resolution rates were also determined. Results: At the 2.1-year followup the incidence rate was 23.9% and the resolution rate was 36.7%. The incidence rate was highest in the oldest group (70 to 78 years) and lowest in the youngest (50 to 54 years), whereas the resolution rate was highest in the group 55 to 59 years old and lowest in the oldest group. Because of the high resolution rate, no reliable incidence rates can be calculated. Despite fluctuation, the prevalence of nocturia increased with age and over time (from 34.4% to 44.7% for the total group, p <0.05). Men who had a frequency-volume chart-nocturnal voiding frequency less than International Prostate Symptom Score-nocturnal voiding frequency (6% of the population) more often had this later on. Conclusions: In this population frequency-volume chart assessed nocturia shows considerable fluctuation. Nevertheless, prevalence increases over time and with increasing age. Men who once had frequency-volume chart-nocturnal voiding frequency less than International Prostate Symptom Score-nocturnal voiding frequency are more likely to have this again. Therefore, frequency-volume charts as well as the International Prostate Symptom Score should be used when evaluating nocturia

Цитокіновий профіль у вагітних з хламідійно-вірусною інфекцією

Урогенитальный хламидиоз и вирусная инфекция – это актуальная медико-социальная проблема, поэтому углубленные исследования клинических, иммунологических и эндокринологических аспектов этой проблемы у беременных, разработка и внедрение лечебно-профилактических программ является одним из перспективных резервов снижения репродуктивных потерь, материнской и перинатальной заболеваемости. Вместе с этим, такие исследования составляют значительный научный интерес и большую практическую ценность. При изучении механизмов осложнений беременности большой интерес вызывают исследования функционального состояния клеток ММС (путем определения уровня провоспалительных цитокинов ИЛ - 1β, ФНО -α), а также Т-лимфоцитов (путем определения провоспалительных цитокинов ИЛ -2, ИФН-γ и провоспалительных цитокинов ИЛ -4, ИЛ -10).Urogenital chlamydia and viral infection are actual medical and social problems. That is why the most promising reserves to reduce reproductive losses, maternal and perinatal morbidity are deep study of clinical, immunological, microbiological and endocrinological aspects of this problem among pregnant women, as well as developing and implementing of health care programs. Moreover, such studies have significant scientific interest and great practical value. While studying the mechanisms of pregnancy complications, the most interesting are the study of the functional state of MMS cells (by determining the level of proinflammatory cytokines IL-1β TNF-α), and T-lymphocytes (by determining the level of proinflammatory cytokines IL-2, IFN-γ and anti-inflammatory cytokines IL-4, IL-10)

Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11

Recurrent chromosomal rearrangements are associated with the development of acute myeloid leukemia (AML). The frequent inversion of chromosome 16 creates the CBFB-MYH11 fusion gene that encodes the fusion protein CBFbeta-SMMHC. This fusion protein inhibits the core-binding factor (CBF), resulting in a block of hematopoietic differentiation, and induces leukemia upon the acquisition of additional mutations. A recent genetic screen identified Plag1 and Plagl2 as CBF beta-SMMHC candidate cooperating proteins. In this study, we demonstrate that Plag1 and Plagl2 independently cooperate with CBF beta-SMMHC in vivo to efficiently trigger leukemia with short latency in the mouse. In addition, Plag1 and Plagl2 increased proliferation by inducing G1 to S transition that resulted in the expansion of hematopoietic progenitors and increased cell renewal in vitro. Finally, PLAG1 and PLAGL2 expression was increased in 20% of human AML samples. Interestingly, PLAGL2 was preferentially increased in samples with chromosome 16 inversion, suggesting that PLAG1 and PLAGL2 may also contribute to human AML. Overall, this study shows that Plag1 and Plagl2 are novel leukemia oncogenes that act by expanding hematopoietic progenitors expressing CbF beta-SMMHC

Integrated management of atrial fibrillation in primary care:results of the ALL-IN cluster randomized trial

Aims To evaluate whether integrated care for atrial. fibrillation (AF) can be safely orchestrated in primary care. Methods and results The ALL-IN trial was a cluster randomized, open-label, pragmatic non-inferiority trial performed in primary care practices in the Netherlands. We randomized 26 practices: 15 to the integrated care intervention and 11 to usual care. The integrated care intervention consisted of (i) quarterly AF check-ups by trained nurses in primary care, also focusing on possibly interfering comorbidities, (ii) monitoring of anticoagulation therapy in primary care, and finally (iii) easy-access availability of consultations from cardiologists and anticoagulation clinics. The primary endpoint was all-cause mortality during 2 years of follow-up. In the intervention arm, 527 out of 941 eligible AF patients aged >65 years provided informed consent to undergo the intervention. These 527 patients were compared with 713 AF patients in the control arm receiving usual care. Median age was 77 (interquartile range 72-83) years. The all-cause mortality rate was 3.5 per 100 patient-years in the intervention arm vs. 6.7 per 100 patient-years in the control arm [adjusted hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.37-0.82]. For non cardiovascular mortality, the adjusted HR was 0.47 (95% CI 0.27-0.82). For other adverse events, no statistically significant differences were observed. Conclusion In this cluster randomized trial, integrated care for elderly AF patients in primary care showed a 45% reduction in all-cause mortality when compared with usual care

Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome

Mutations in CCAAT/enhancer binding protein α (CEBPA) are seen in 5% to 14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry 2 mutations (CEBPAdouble-mut), usually biallelic, whereas single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high-performance liquid chromatography and nucleotide sequencing, we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases (28 CEBPAdouble-mut and 13 CEBPA single-mut cases) CEBPAdouble-mut associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multi-variable analysis that included cytoge-netic risk, FZT3-ITD and NPM1 mutation, white blood cell count, and age. In contrast, CEBPA single-mut AMLs did not express a discriminating signature and could not be distinguished from wild-type cases as regards clinical outcome. These results demonstrate significant underlying heterogeneity within CEBPA mutation-positive AML with prognostic relevance

Initial results of secukinumab drug survival in patients with psoriasis: A multicentre daily practice cohort study

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan–Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice

Phosphorylation of the Leukemic Oncoprotein EVI1 on Serine 196 Modulates DNA Binding, Transcriptional Repression and Transforming Ability

The EVI1 (ecotropic viral integration site 1) gene at 3q26 codes for a transcriptional regulator with an essential role in haematopoiesis. Overexpression of EVI1 in acute myeloid leukaemia (AML) is frequently associated with 3q26 rearrangements and confers extremely poor prognosis. EVI1 mediates transcriptional regulation, signalling, and epigenetic modifications by interacting with DNA, proteins and protein complexes. To explore to what extent protein phosphorylation impacts on EVI1 functions, we analysed endogenous EVI1 protein from a high EVI1 expressing Fanconi anaemia (FA) derived AML cell line. Mass spectrometric analysis of immunoprecipitated EVI1 revealed phosphorylation at serine 196 (S196) in the sixth zinc finger of the N-terminal zinc finger domain. Mutated EVI1 with an aspartate substitution at serine 196 (S196D), which mimics serine phosphorylation of this site, exhibited reduced DNA-binding and transcriptional repression from a gene promotor selectively targeted by the N-terminal zinc finger domain. Forced expression of the S196D mutant significantly reduced EVI1 mediated transformation of Rat1 fibroblasts. While EVI1-mediated serial replating of murine haematopoietic progenitors was maintained by EVI1-S196D, this was associated with significantly higher Evi1-trancript levels compared with WT-EVI1 or EVI1-S196A, mimicking S196 non-phosphorylated EVI1. These data suggest that EVI1 function is modulated by phosphorylation of the first zinc finger domain

Initial Results of Secukinumab Drug Survival in Patients with Psoriasis:A Multicentre Daily Practice Cohort Study

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials (RCTs). However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least 1 episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practic

What predicts incident nocturia? A population-based study in older men: The Krimpen study

INTRODUCTION AND OBJECTIVES: Many conditions and characteristics are associated with nocturia, however, there is a paucity of data on the factors that predict the development of nocturia. We therefore determined factors predictive of incident nocturia. METHODS: We analyzed the database of a population-based cohort study among 1,688 men aged 50-78 years old, without radical prostatectomy, transurethral surgery, or bladder or prostate cancer, living in Krimpen aan den IJssel, The Netherlands. Data were obtained using frequency-volume charts (FVC), from which the nocturnal voiding frequency (NVF) was determined. Nocturia was defined as NVF ≥ 2. Conditions and characteristics were determined via medical examination and a 113-item questionnaire. Men without nocturia at baseline (BL) and no exclusion criteria met were selected. At the first follow-up round (FU-1; after 2.1 years) we determined how many men developed nocturia. Univariable analyses were done to determine the association between the BL characteristics and nocturia-status at FU-1. Variables with an association p <0.25 were selected to create a multivariable logistic regression model. After a manual backward selection procedure a final model was created with only significant associations (p¡ü0.05). RESULTS: At BL 1597 men completed an FVC, 133 men met the exclusion criteria. 342 men were excluded because of missing sleeping-hours, and 386 men had nocturia (34.4%), resulting in a target population of 736 men. At FU-1, 341 men were excluded because they did not void during the night or within the first hour of rising, did not complete a FVC, or due to loss to follow up. Therefore, analysis could was possible in 395 men. These men did not significantly differ from the total population regarding conditions and characteristics. Median age was 59.8, the incidence-rate after 2.1 years for nocturia was 24.8%. Table 1 shows the univariable and multivariable logistic regression models. Univariably as well as in the final model only age and alcohol intake were significantly related to incident nocturia. CONCLUSIONS: Although many characteristics are associated with nocturia, only age could significantly predict incident nocturia. Alcohol intake had a protective effect. (Table presented)

The Natural History and Predictive Factors of Voided Volume in Older Men: The Krimpen Study

Purpose: Although functional bladder capacity, as expressed by maximum voided volume and other frequency-volume chart parameters, are important determinants of lower urinary tract symptoms, to our knowledge no population based data are available on changes in voided volume. We determined changes in and determinants of voided volume and voiding frequency with advancing age and with time, as measured by frequency-volume charts. Materials and Methods: We performed a longitudinal, population based study in 1,688 men 50 to 78 years old with followup at 2.1, 4.2 and 6.5 years. Data were obtained using frequency-volume charts for maximum, 24-hour and average voided volume, and 24-hour voiding frequency as well as physical and urological measurements, and self-administered questionnaires. We used a linear mixed effect model to determine factors predicting volume changes. Results: Median maximum and average voided volume decreased with time from 400 to 380 and 245 to 240 ml, respectively, and were smaller in older age groups while 24-hour voided volume showed no change. The 24-hour voiding frequency increased with time and with advancing age. Maximum, 24-hour and average voided volumes were positively related to alcohol intake. Maximum and average voided volumes were negatively related to higher age at baseline and the passage of time. Hypertension, diuretics and post-void residual volume were related to higher 24-hour voided volume. Conclusions: In older men maximum and average voided volume show a small but statistically significant decrease with time and with advancing age while 24-hour voided volume does not. Factors predicting the change in maximum or average voided volume are alcohol intake and higher age