Model prediction of subendocardial perfusion of the coronary circulation in the presence of an epicardial coronary artery stenosis

The subendocardium is most vulnerable to ischemia, which is ameliorated by relaxation during diastole and increased coronary pressure. Recent clinical techniques permit the measuring of subendocardial perfusion and it is therefore important to gain insight into how measurements depend on perfusion conditions of the heart. Using data from microsphere experiments a layered model of the myocardial wall was developed. Myocardial perfusion distribution during hyperemia was predicted for different degrees of coronary stenosis and at different levels of Diastolic Time Fraction (DTF). At the reference DTF, perfusion was rather evenly distributed over the layers and the effect of the stenosis was homogenous. However, at shorter or longer DTF, the subendocardium was the first or last to suffer from shortage of perfusion. It is therefore concluded that the possible occurrence of subendocardial ischemia at exercise is underestimated when heart rate is increased and DTF is lower

PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690]

BACKGROUND: During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. AIM: The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. DESIGN: Seventy-five (3 × 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out

Three-year survival of single- and two-surface ART restorations in a high-caries child population

The aim of this study was to evaluate the survival of single- and two-surface atraumatic restorative treatment (ART) restorations in the primary and permanent dentitions of children from a high-caries population, in a field setting. The study was conducted in the rainforest of Suriname, South America. ART restorations, made by four Dutch dentists, were evaluated after 6 months, 1, 2, and 3 years. Four hundred seventy-five ART restorations were placed in the primary dentition and 54 in first permanent molars of 194 children (mean age 6.09 ± 0.48 years). Three-year cumulative survivals of single- and two-surface ART restorations in the primary dentition were 43.4 and 12.2%, respectively. Main failure characteristics were gross marginal defects and total or partial losses. Three-year cumulative survival for single-surface ART restorations in the permanent dentition was 29.6%. Main failure characteristics were secondary caries and gross marginal defects. An operator effect was found only for two-surface restorations. The results show extremely low survival rates for single- and two-surface ART restorations in the primary and permanent dentitions. The variable success for ART may initiate further discussion about alternative treatment strategies, especially in those situations where choices have to be made with respect to a well-balanced, cost-effective package of basic oral health care

The effect of a complementary e-learning course on implementation of a quality improvement project regarding care for elderly patients: a stepped wedge trial

<p>Abstract</p> <p>Background</p> <p>Delirium occurs frequently in elderly hospitalised patients and is associated with higher mortality, increased length of hospital stay, functional decline, and admission to long-term care. Healthcare professionals frequently do not recognise delirium, indicating that education can play an important role in improving delirium care for hospitalised elderly. Previous studies have indicated that e-learning can provide an effective way of educating healthcare professionals and improving quality of care, though results are inconsistent.</p> <p>Methods and design</p> <p>This stepped wedge cluster randomised trial will assess the effects of a complementary delirium e-learning course on the implementation of quality improvement initiative, which aims to enhance the recognition and management of delirium in elderly patients. The trial will be conducted in 18 Dutch hospitals and last 11 months. Measurements will be taken in all participating wards using monthly record reviews, in order to monitor delivered care. These measurements will include the percentage of elderly patients who were screened for the risk of developing delirium, use of the Delirium Observation Screening scale, use of nursing or medical interventions, and the percentage of elderly patients who were diagnosed with delirium. Data regarding the e-learning course will be gathered as well. These data will include user characteristics, information regarding use of the course, delirium knowledge before and after using the course, and the attitude and intentions of nurses concerning delirium care.</p> <p>Setting</p> <p>The study will be conducted in internal medicine and surgical wards of eighteen hospitals that are at the beginning stages of implementing the Frail Elderly Project in the Netherlands.</p> <p>Discussion</p> <p>Better recognition of elderly patients at risk for delirium and subsequent care is expected from the introduction of an e-learning course for nurses that is complementary to an existing quality improvement project. This trial has the potential to demonstrate that e-learning can be a vital part of the implementation process, especially for quality improvement projects aimed at complex health issues such as delirium. The study will contribute to a growing body of knowledge concerning e-learning and the effects it can have on knowledge as well as delivered care.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2885">NTR2885</a></p

PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN 74418480]

BACKGROUND: In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3°C (95% CI: 0.1–0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. METHODS/DESIGN: Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one

Untreated severe dental decay: a neglected determinant of low Body Mass Index in 12-year-old Filipino children

Contains fulltext : 98500.pdf (publisher's version ) (Open Access)BACKGROUND: Dental decay is the most common childhood disease worldwide and most of the decay remains untreated. In the Philippines caries levels are among the highest in the South East Asian region. Elementary school children suffer from high prevalence of stunting and underweight.The present study aimed to investigate the association between untreated dental decay and Body Mass Index (BMI) among 12-year-old Filipino children. METHODS: Data collection was part of the National Oral Health Survey, a representative cross-sectional study of 1951 11-13-year-old school children using a modified, stratified cluster sampling design based on population classifications of the Philippine National Statistics Office. Caries was scored according to WHO criteria (1997) and odontogenic infections using the PUFA index. Anthropometric measures were performed by trained nurses. Some socio-economic determinants were included as potential confounding factors. RESULTS: The overall prevalence of caries (DMFT + dmft > 0) was 82.3% (95%CI; 80.6%-84.0%). The overall prevalence of odontogenic infections due to caries (PUFA + pufa > 0) was 55.7% (95% CI; 53.5%-57.9%) The BMI of 27.1% (95%CI; 25.1%-29.1%) of children was below normal, 1% (95%CI; 0.5%-1.4%) had a BMI above normal. The regression coefficient between BMI and caries was highly significant (p 0) as compared to those without odontogenic infections had an increased risk of a below normal BMI (OR: 1.47; 95% CI: 1.19-1.80). CONCLUSIONS: This is the first-ever representative survey showing a significant association between caries and BMI and particularly between odontogenic infections and below normal BMI. An expanded model of hypothesised associations is presented that includes progressed forms of dental decay as a significant, yet largely neglected determinant of poor child development

Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor

Antidepressants increase adult hippocampal neurogenesis in animal models, but the underlying molecular mechanisms are unknown. In this study, we used human hippocampal progenitor cells to investigate the molecular pathways involved in the antidepressant-induced modulation of neurogenesis. Because our previous studies have shown that antidepressants regulate glucocorticoid receptor (GR) function, we specifically tested whether the GR may be involved in the effects of these drugs on neurogenesis. We found that treatment (for 3–10 days) with the antidepressant, sertraline, increased neuronal differentiation via a GR-dependent mechanism. Specifically, sertraline increased both immature, doublecortin (Dcx)-positive neuroblasts (+16%) and mature, microtubulin-associated protein-2 (MAP2)-positive neurons (+26%). This effect was abolished by the GR-antagonist, RU486. Interestingly, progenitor cell proliferation, as investigated by 5′-bromodeoxyuridine (BrdU) incorporation, was only increased when cells were co-treated with sertraline and the GR-agonist, dexamethasone, (+14%) an effect which was also abolished by RU486. Furthermore, the phosphodiesterase type 4 (PDE4)-inhibitor, rolipram, enhanced the effects of sertraline, whereas the protein kinase A (PKA)-inhibitor, H89, suppressed the effects of sertraline. Indeed, sertraline increased GR transactivation, modified GR phosphorylation and increased expression of the GR-regulated cyclin-dependent kinase-2 (CDK2) inhibitors, p27Kip1 and p57Kip2. In conclusion, our data suggest that the antidepressant, sertraline, increases human hippocampal neurogenesis via a GR-dependent mechanism that requires PKA signaling, GR phosphorylation and activation of a specific set of genes. Our data point toward an important role for the GR in the antidepressant-induced modulation of neurogenesis in humans