Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response

Background: Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT<sub>2A</sub> receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT<sub>2A</sub>/D<sub>4</sub> antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect. Method: An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out. Results: The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery–Asberg Depression Rating Scale (MADRS) score of 32.6 (S.D.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression–Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002). Conclusions: Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week

Predicting dementia from primary care records: a systematic review and meta-analysis

Introduction Possible dementia is usually identified in primary care by general practitioners (GPs) who refer to specialists for diagnosis. Only two-thirds of dementia cases are currently recorded in primary care, so increasing the proportion of cases diagnosed is a strategic priority for the UK and internationally. Clinical entities in the primary care record may indicate risk of developing dementia, and could be combined in a predictive model to help find patients who are missing a diagnosis. We conducted a meta-analysis to identify clinical entities with potential for use in such a predictive model for dementia in primary care. Methods and Findings We conducted a systematic search in PubMed, Web of Science and primary care database bibliographies. We included cohort or case-control studies which used routinely collected primary care data, to measure the association between any clinical entity and dementia. Meta-analyses were performed to pool odds ratios. A sensitivity analysis assessed the impact of non-independence of cases between studies. From a sift of 3836 papers, 20 studies, all European, were eligible for inclusion, comprising >1 million patients. 75 clinical entities were assessed as risk factors for all cause dementia, Alzheimer’s (AD) and Vascular dementia (VaD). Data included were unexpectedly heterogeneous, and assumptions were made about definitions of clinical entities and timing as these were not all well described. Meta-analysis showed that neuropsychiatric symptoms including depression, anxiety, and seizures, cognitive symptoms, and history of stroke, were positively associated with dementia. Cardiovascular risk factors such as hypertension, heart disease, dyslipidaemia and diabetes were positively associated with VaD and negatively with AD. Sensitivity analyses showed similar results. Conclusions These findings are of potential value in guiding feature selection for a risk prediction tool for dementia in primary care. Limitations include findings being UK-focussed. Further predictive entities ascertainable from primary care data, such as changes in consulting patterns, were absent from the literature and should be explored in future studies

The importance of imprinting in the human placenta.

As a field of study, genomic imprinting has grown rapidly in the last 20 years, with a growing figure of around 100 imprinted genes known in the mouse and approximately 50 in the human. The imprinted expression of genes may be transient and highly tissue-specific, and there are potentially hundreds of other, as yet undiscovered, imprinted transcripts. The placenta is notable amongst mammalian organs for its high and prolific expression of imprinted genes. This review discusses the development of the human placenta and focuses on the function of imprinting in this organ. Imprinting is potentially a mechanism to balance parental resource allocation and it plays an important role in growth. The placenta, as the interface between mother and fetus, is central to prenatal growth control. The expression of genes subject to parental allelic expression bias has, over the years, been shown to be essential for the normal development and physiology of the placenta. In this review we also discuss the significance of genes that lack conservation of imprinting between mice and humans, genes whose imprinted expression is often placental-specific. Finally, we illustrate the importance of imprinting in the postnatal human in terms of several human imprinting disorders, with consideration of the brain as a key organ for imprinted gene expression after birth

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807

Principal component analysis for studying the world security problem

This research is a continuation of the work [1], in which the list of ten most essential global threats to the future of mankind have been presented. The initial data on each threat are taken from the respectable international organizations data bases. Then, we defined the summarized impact of the examined ten global threats totality on different countries based on cluster analysis method with the purpose of selecting groups of the countries with “close” performances of summarized threats. By using the Minkovsky type metric the foresight of the future global conflicting has been executed. To facilitate the analysis and make it easier we use the method of Principal Component Analysis (PCA) which allows reduce variables with many properties to several hidden factors. The analysis shows that currently the most considerable threats for most countries are the reduction of energy security, worsening of balance between bio capacity and human demands and the incomes inequality between people and countries.Проведено дослідження національної безпеки різних країн світу з використанням метода головних компонент (Principal Component Analysis) у просторі десяти глобальних загроз. За допомогою обчислення коефіцієнтів кореляції визначено характер залежності між головними чинниками і вихідними загрозами. Визначено три найбільш істотні загрози, які впливають на національну безпеку більшості країн світу: державна нестабільність, дефіцит енергетичних ресурсів і нерівність доходів (Gini Index). Виконано графічну інтерпретацію глобальних загроз і визначено міри залежності між їх основними групами.Проведено исследование национальной безопасности различных стран мира с использованием метода главных компонент (Principal Component Analysis) в пространстве десяти глобальных угроз. С помощью вычисления коэффициентов корреляции определен характер зависимости между главными факторами и исходными угрозами. Проведена кластеризация стран по уровню глобальных угроз. Определены три наиболее существенные угрозы, влияющие на национальную безопасность большинства стран мира: государственная нестабильность, дефицит энергетических ресурсов и неравенство доходов (Gini Index). Выполнена графическая интерпретация глобальных угроз в пространстве трех главных компонент. Проведено исследование факторной структуры угроз и определены степени зависимости между их основными группами

Reliability and Validity of the Supports Intensity Scale (SIS) Measured in Adults with Physical Disabilities

The objective of this study was to investigate the internal consistency and the construct validity of the Dutch version of the Supports Intensity Scale (SIS-NL1.0; Buntinx 2006) in individuals with physical disabilities (N = 65). To investigate the construct validity, the relationship between SIS subscales and practical skills (Barthel Index; BI) was calculated. Support was provided for the internal consistency. The SIS subscales (except Behavior) had moderate to high intercorrelations and the SIS was able to discriminate between groups with different number of disabilities. However, weak relationships were found between the BI and four out of eight SIS subscales. For people with physical disabilities, future revisions of the SIS should also take into consideration limitations in practical skills in other support domains

Efecto de la frecuencia de amamantamiento sobre el comportamiento productivo y el balance del nitrógeno en cabritos

Se realizó un trabajo con 15 cabritos lactantes, sujetos a crianza artificial, para evaluar tres frecuencias de amamantamiento y los correspondientes consumos máximos obtenibles, así como el uso del nitrógeno (N) lácteo, midiendo la retención del mismo

Dietary intake of micronutrients and the risk of developing bladder cancer: results from the Belgian case–control study on bladder cancer risk

OBJECTIVE: We aimed to investigate the effect of dietary intake of micronutrients that are metabolized and excreted via the urinary tract on bladder cancer risk. METHODS: A semi-quantitative 322 item food frequency questionnaire (FFQ) was used to collect dietary data from 200 bladder cancer cases and 386 control subjects participating in the Belgian case-control study on bladder cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age, sex, smoking characteristics, occupational exposures, and energy intake. RESULTS: We observed a positive association between calcium intake and bladder cancer (OR: 1.77; 95% CI: 1.00-3.15; p-trend = 0.049) and increased odds, although not statistically significant, for highest tertile of phosphorus intake (OR: 1.82; 95% CI: 0.95-3.49; p-trend = 0.06). We identified possible modification of the effects of both calcium and phosphorus by level of magnesium intake. Increased odds of bladder cancer were also observed for participants with highest intake of phosphorus and lowest intake of vitamin D (OR: 4.25; 95% CI: 1.44-12.55) and among older participants with the highest intakes of calcium (OR: 1.90; 95% CI: 1.08-3.36) and phosphorus (OR: 2.02; 95% CI: 1.05-3.92). CONCLUSION: The positive associations we observed between bladder cancer and intake of calcium and phosphorus require confirmation by other studies. The balances between inter-related micronutrients also warrant further examination