Change in Prescribing forSecondary Prevention of Stroke and Coronary Heart Disease in Finnish Nursing Homes and Assisted Living Facilities

BackgroundOne quarter of residents in long-term care facilities (LTCFs) have a diagnosis of CHD or stroke and over half use at least one preventative cardiovascular medication. There have been no studies that have investigated the longitudinal change in secondary preventative cardiovascular medication use in residents in LTCFs over time.ObjectiveThe aim of this study was to investigate the change in cardiovascular medication use among residents with coronary heart disease (CHD) and prior stroke in nursing homes (NHs) and assisted living facilities (ALFs) in Finland over time, and whether this change differs according to dementia status.MethodsThree comparable cross-sectional audits of cardiovascular medication use among residents aged 65years and over with CHD or prior stroke in NHs in 2003 and 2011 and ALFs in 2007 and 2011 were compared. Logistic regression analyses adjusted for gender, age, mobility, cancer and length of stay were performed to examine the effect of study year, dementia and their interaction on medication use.ResultsCardiovascular medication use among residents with CHD (NHs: 89% vs 70%; ALFs: 89% vs 84%) and antithrombotic medication use among residents with stroke (NHs: 72% vs 63%; ALFs: 78% vs 69%) declined between 2003 and 2011 in NHs and 2007 and 2011 in ALFs.Decline in the use of diuretics, nitrates and digoxin were found in both groups and settings. Cardiovascular medication use among residents with CHD and dementia declined in NHs (88% [95% CI 85-91] in 2003 vs 70% [95% CI 64-75] in 2011) whereas there was no change among people without dementia. There was no change in cardiovascular medication use among residents with CHD in ALFs with or without dementia over time. Antithrombotic use was lower in residents with dementia compared with residents without dementia in NHs (pPeer reviewe

The Design of a Best Execution Market

The notion of best execution on securities markets is manifold. Best execution has different meanings to different market participants, therefore, it is difficult to find a unique market structure that meets this requirements for all the participants. Traditional market structures are either static or flexible, meaning that an individual market participant has no influence regarding the concrete market structure’s characteristics, like e. g. the price discovery mechanism, trading frequency or the market transparency. Traditional market structures are either static or flexible, meaning that an individual market participant has no influence regarding the Focussing on customer orientation, we propose a new type of market structure: the dynamic market model, where participants individually choose the characteristics of the market structure for each transaction they perform. Furthermore, this paper offers an approach to design dynamic market models from scratch. We briefly sketch the necessary steps towards a dynamic market model. Traditional market structures are either static or flexible, meaning that an individual market participant has no influence regarding the Finally, we present AMTRAS; the prototype of an electronic trading system that was conceived and implemented following the aforementioned approach. AMTRAS is an software-agent based bond trading system designed for the need of institutional investors. It implements a dynamic market model, a sophisticated product- and partner matching scheme as well as an innovative price discovery approach

Patterns of High-Dose and Long-Term Proton Pump Inhibitor Use: A Cross-Sectional Study in Six South Australian Residential Aged Care Services

Aim: While proton pump inhibitors (PPIs) are generally considered safe and well tolerated, frail older people who take PPIs long term may be susceptible to adverse events. This study characterized PPI use and determined factors associated with high-dose use among older adults in residential aged care services (RACSs).Methods: A cross-sectional study of 383 residents of six South Australian RACSs within the same organization was conducted. Clinical, diagnostic, and medication data were collected by study nurses. The proportions of residents who took a PPI for > 8 weeks and without documented indications were calculated. Factors associated with high-dose PPI use compared to standard/low doses were identified using age- and sex-adjusted logistic regression models.Results: 196 (51%) residents received a PPI, with 45 (23%) prescribed a high dose. Overall, 173 (88%) PPI users had documented clinical indications or received medications that can increase bleeding risk. Three-quarters of PPI users with gastroesophageal reflux disease or dyspepsia had received a PPI for > 8 weeks. High-dose PPI use was associated with increasing medication regimen complexity [odds ratio (OR) 1.02; 95% confidence interval (CI) 1.01–1.04 per one-point increase in Medication Regimen Complexity Index score] and a greater number of medications prescribed for regular use (OR 1.11; 95% CI 1.01–1.21 per additional medication).Conclusions: Half of all residents received a PPI, of whom the majority had documented clinical indications or received medications that may increase bleeding risk. There remains an opportunity to review the continuing need for treatment and consider “step-down” approaches for high-dose PPI users.</p

Prescribing patterns of low doses of antipsychotic medications in older Asian patients with schizophrenia, 2001-2009

Background: This study examined the use of low doses of antipsychotic medications (300mg/day CPZeq or less) in older Asian patients with schizophrenia and its demographic and clinical correlates. Methods: Information on hospitalized patients with schizophrenia, aged 55 years or older, was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001-2009). Data on 1,452 patients in eight Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India, and Malaysia were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure. Results: The prescription frequency for low doses of antipsychotic medications was 40.9% in the pooled sample. Multiple logistic regression analysis of the whole sample showed that patients on low doses of antipsychotic medications were more likely to be female, have an older age, a shorter length of illness, and less positive symptoms. Of patients in the six countries and territories that participated in all the surveys between 2001 and 2009, those in Japan were less likely to receive low doses of antipsychotics. Conclusion: Low doses of antipsychotic medications were only applied in less than half of older Asian patients with schizophreni

Mediator Acts Upstream of the Transcriptional Activator Gal4

We show that Mediator, a protein originally isolated on the basis of its ability to respond to transcriptional activators, and thought to be regulated by an activator, can also be the master that controls the activator

Expression signatures of TP53 mutations in serous ovarian cancers

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>TP53 </it>gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease.</p> <p>Methods</p> <p>The <it>TP53 </it>coding region was sequenced in 89 frozen serous ovarian cancers, 40 early stage (I/II) and 49 advanced stage (III/IV). Affymetrix U133A expression data was used to define gene expression patterns by mutation, type of mutation, and cancer stage.</p> <p>Results</p> <p>Missense or chain terminating (null) mutations in <it>TP53 </it>were found in 59/89 (66%) ovarian cancers. Early stage cancers had a significantly higher rate of null mutations than late stage disease (38% vs. 8%, p < 0.03). In advanced stage cases, mutations were more prevalent in short term survivors than long term survivors (81% vs. 30%, p = 0.0004). Gene expression patterns had a robust ability to predict <it>TP53 </it>status within training data. By using early versus late stage disease for out of sample predictions, the signature derived from early stage cancers could accurately (86%) predict mutation status of late stage cancers.</p> <p>Conclusions</p> <p>This represents the first attempt to define a genomic signature of <it>TP53 </it>mutation in ovarian cancer. Patterns of gene expression characteristic of <it>TP53 </it>mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of <it>TP53 </it>mutation in breast cancer.</p

Experimental Inoculation of Juvenile Rhesus Macaques with Primate Enteric Caliciviruses

Tissue culture-adapted Tulane virus (TV), a GI.1 rhesus enteric calicivirus (ReCV), and a mixture of GII.2 and GII.4 human norovirus (NoV)-containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta) in order to evaluate infection caused by these viruses. METHODOLOGY & FINDINGS: Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN) serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV-inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen-positive (TV+) cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin--an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs) from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen-containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05) suggested active TV replication in cultured lymphocytes.Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability