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

Chronic Diseases among Older Cancer Survivors

Objective. To compare the occurrence of pre-existing and subsequent comorbidity among older cancer patients (≥60 years) with older non-cancer patients. Material and Methods. Each cancer patient (n=3835, mean age 72) was matched with four non-cancer patients in terms of age, sex, and practice. The occurrence of chronic diseases was assessed cross-sectionally (lifetime prevalence at time of diagnosis) and longitudinally (incidence after diagnosis) for all cancer patients and for breast, prostate, and colorectal cancer patients separately. Cancer and non-cancer patients were compared using logistic and Cox regression analysis. Results. The occurrence of the most common pre-existing and incident chronic diseases was largely similar in cancer and non-cancer patients, except for pre-existing COPD (OR 1.21, 95% CI 1.06–1.37) and subsequent venous thrombosis in the first two years after cancer diagnosis (HR 4.20, 95% CI 2.74–6.44), which were significantly more frequent (P<0.01) among older cancer compared to non-cancer patients. Conclusion. The frequency of multimorbidity in older cancer patients is high. However, apart from COPD and venous thrombosis, the incidence of chronic diseases in older cancer patients is similar compared to non-cancer patients of the same age, sex, and practice

Understanding the Relationship between Quality of Life, Adaptive Behavior and Support Needs

Psychometric tools providing quantitative measures of the constructs of adaptive behavior, support needs, and quality of life (QOL) have received considerable attention within the field of intellectual disability (ID). The relationship between the three constructs was investigated by examining scores on the Adaptive Behavior Scale (ABS), Supports Intensity Scale (SIS), and Personal Outcomes Scale (POS; a QOL scale). Data from 146 Portuguese adults with ID revealed that: (a) the ABS domains showed a moderate negative relationship with the SIS subscales; (b) the absolute value of correlations between SIS/ABS domains were greater than either the ABS/POS or SIS/POS correlations; and (c) people with relatively stronger adaptive skills and less intense support needs experience a higher QOL. Additionally, adaptive behavior scores were a stronger predictor of personal outcomes than the support needs scores. Personal outcomes associated with QOL were similar when assessed by the POS through self-report and report-of-others measures. Implications for future research and practice are discussed.<br/

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

Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences

BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995-2006 . The carcinoma in situ incidence increased 1.7-fold during 1995-2000, and decreased by 19.6% during 2000-2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer

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

Chronic Pancreas Allograft Rejection Followed by Successful HLA-Incompatible Islet Alloautotransplantation:A Novel Strategy?

The purpose of pancreas or islet transplantation is to restore glycemic control in order to mitigate diabetes-related complications and prevent severe hypoglycemia. Complications from chronic pancreas allograft rejection may lead to transplantectomy, even when the endocrine function remains preserved. We present first evidence of a successful HLA incompatible islet re-transplantation with islets isolated from a rejecting pancreas allograft after simultaneous kidney pancreas transplantation. The pancreas allograft was removed because of progressively painful pancreatic panniculitis from clinically uncontrolled chronic rejection. The endocrine function was preserved. Induction treatment for this “islet alloautotransplantation” consisted of plasmapheresis, IVIg and alemtuzumab. At 1 year, the patient retained islet graft function with good glycemic control and absence of severe hypoglycemia, despite persistent low-grade HLA donor-specific antibodies. His panniculitis had resolved completely. In our point of view, islet alloautotransplantation derived from a chronically rejecting pancreas allograft is a potential option to salvage (partial) islet function, despite preformed donor-specific antibodies, in order to maintain stable glycemic control. Thereby it protects against severe hypoglycemia, and it potentially mitigates kidney graft dysfunction and other diabetes-related complications in patients with continued need for immunosuppression and who are otherwise difficult to retransplant.</p

Chronic Pancreas Allograft Rejection Followed by Successful HLA-Incompatible Islet Alloautotransplantation:A Novel Strategy?

The purpose of pancreas or islet transplantation is to restore glycemic control in order to mitigate diabetes-related complications and prevent severe hypoglycemia. Complications from chronic pancreas allograft rejection may lead to transplantectomy, even when the endocrine function remains preserved. We present first evidence of a successful HLA incompatible islet re-transplantation with islets isolated from a rejecting pancreas allograft after simultaneous kidney pancreas transplantation. The pancreas allograft was removed because of progressively painful pancreatic panniculitis from clinically uncontrolled chronic rejection. The endocrine function was preserved. Induction treatment for this “islet alloautotransplantation” consisted of plasmapheresis, IVIg and alemtuzumab. At 1 year, the patient retained islet graft function with good glycemic control and absence of severe hypoglycemia, despite persistent low-grade HLA donor-specific antibodies. His panniculitis had resolved completely. In our point of view, islet alloautotransplantation derived from a chronically rejecting pancreas allograft is a potential option to salvage (partial) islet function, despite preformed donor-specific antibodies, in order to maintain stable glycemic control. Thereby it protects against severe hypoglycemia, and it potentially mitigates kidney graft dysfunction and other diabetes-related complications in patients with continued need for immunosuppression and who are otherwise difficult to retransplant.</p

Are Type, Frequency, and Daily Time Equally Valid Estimators of Support Needs in Children With Intellectual Disability? A Multitrait?Multimethod Analysis of the Supports Intensity Scale for Children (SIS-C)

ABSTRACT: Support needs represent the intensity of support required by a person with a disability in order to take part in the activities related to normative human functioning. The Supports Intensity Scale for Children (SIS-C) is possibly the most promising tool for assessing and designing individualized support programs in children with intellectual disability. The SIS-C measures support needs across 61 activities, each one assessed along three methods: type of support, frequency, and daily time during which support is to be given. We investigated the impact of method effects in the SIS-C through a bifactor approach to the analysis of multitrait?multimethod matrices. The results suggest that neither intensity nor frequency scales produced method effects that significantly distorted the measurement of support needs. However, the daily support time method had substantial undesirable effects on five of the seven subscales of support needs. Considerations about support needs assessment and future modifications of the scale are discussed.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Work on this research was funded by the Spanish Ministry of the Economy and Competitiveness (R&D Projects, PSI2012- 36278), and the Autonomous Community of Castile and Leon (R&D Projects, SA120U13)