Chance of aneurysm in patients suspected of SAH who have a ‘negative’ CT scan but a ‘positive’ lumbar puncture

In patients with sudden severe headache and a negative computed tomography (CT) scan, a lumbar puncture (LP) is performed to rule in or out a subarachnoid haemorrhage (SAH), but this procedure is under debate. In a hospital-based series of 30 patients with sudden headache, a negative CT scan but a positive LP (defined as detection of bilirubin >0.05 at wavelength 458 nm), we studied the chance of harbouring an aneurysm and the clinical outcome. Aneurysms were found in none of both patients who presented within 3 days, in 8 of the 18 (44%) who presented within 4–7 days and in 5 of the 10 (50%) who presented within 8–14 days. Of the 13 patients with an aneurysm, 3 (23%) had poor outcome. In patients who present late after sudden headache, the yield in terms of aneurysms is high in those who have a positive lumbar puncture. In patients with an aneurysm as cause of the positive lumbar puncture, outcome is in the same range as in SAH patients admitted in good clinical condition

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

Circulating Apoptotic Progenitor Cells in Patients with Congestive Heart Failure

Background: Circulating CD34+ endothelial progenitor cells (EPCs) are capable of differentiating into mature endothelial cells to assist in angiogenesis and vasculogenesis. We sought to quantify the numbers of apoptotic progenitors in patients with congestive heart failure. Methods and Results: Peripheral blood mononuclear cells were isolated by Ficoll density-gradient from 58 patients with various degrees of heart failure and 23 matched controls. Apoptosis in progenitor CD34+ cells was assessed using the Annexin V-PE/PI detection kit, and FACS analysis was performed with triple staining for CD34, annexin-V and propidium iodide. The percentage of early and late apoptotic progenitor cells was determined in the subject groups and was correlated with clinical characteristics. While there was no significant difference in total CD34 positive cells or early apoptotic progenitors between control subjects and CHF patients (p = 0.42) or between severe and mild/moderate CHF groups (p = 0.544), there was an elevated number of late apoptotic progenitors in the severe CHF group compared with the mild/moderate CHF group (p = 0.03). Late apoptotic progenitors were significantly increased in CHF patients as compared to matched controls. There was also an inverse correlation between late apoptotic progenitors and ejection fraction (r = 20.252, p = 0.028) as well as a positive association with NYHA class (r = 0.223, p = 0.046). Conclusion: Severe heart failure patients exhibited higher numbers of late apoptotic progenitors, and this was positivel

Circulating CD62E+ Microparticles and Cardiovascular Outcomes

BACKGROUND: Activated endothelial cells release plasma membrane submicron vesicles expressing CD62E (E-selectin) into blood, known as endothelial microparticles (EMPs). We studied whether the levels of endothelial microparticles expressing CD62E(+), CD31(+)/Annexin-V(+), or CD31(+)/CD42(-) predict cardiovascular outcomes in patients with stroke history. METHODS/PRINCIPAL FINDINGS: Patients with stroke history at least 3 months prior to enrolment were recruited. Peripheral blood EMP levels were measured by flow cytometry. Major cardiovascular events and death were monitored for 36 months. Three hundred patients were enrolled, of which 298 completed the study according to protocol. Major cardiovascular events occurred in 29 patients (9.7%). Nine patients died, five from cardiovascular causes. Cumulative event-free survival rates were lower in patients with high levels of CD62E(+) microparticles. Multivariate Cox regression analysis adjusted for cardiovascular risk factors, medications and stroke etiologic groups showed an association between a high CD62E(+) microparticle level and a risk of major cardiovascular events and hospitalization. Levels of other kinds of EMPs expressing CD31(+)/Annexin-V(+) or CD31(+)/CD42(-) markers were not predictive of cardiovascular outcomes. CONCLUSION: A high level of CD62E(+) microparticles is associated with cardiovascular events in patients with stroke history, suggesting that the systemic endothelial activation increases the risk for cardiovascular morbidities

Loss of estrogen receptor β decreases mitochondrial energetic potential and increases thrombogenicity of platelets in aged female mice

Platelets derived from aged (reproductively senescent) female mice with genetic deletion of estrogen receptor beta (βER) are more thrombogenic than those from age-matched wild-type (WT) mice. Intracellular processes contributing to this increased thrombogenicity are not known. Experiments were designed to identify subcellular localization of estrogen receptors and evaluate both glycolytic and mitochondrial energetic processes which might affect platelet activation. Platelets and blood from aged (22–24 months) WT and estrogen receptor β knockout (βERKO) female mice were used in this study. Body, spleen weight, and serum concentrations of follicle-stimulating hormone and 17β-estradiol were comparable between WT and βERKO mice. Number of spontaneous deaths was greater in the βERKO colony (50% compared to 30% in WT) over the course of 24 months. In resting (nonactivated) platelets, estrogen receptors did not appear to colocalize with mitochondria by immunostaining. Lactate production and mitochondrial membrane potential of intact platelets were similar in both groups of mice. However, activities of NADH dehydrogenase, cytochrome bc1 complex, and cytochrome c oxidase of the electron transport chain were reduced in mitochondria isolated from platelets from βERKO compared to WT mice. There were a significantly higher number of phosphatidylserine-expressing platelet-derived microvesicles in the plasma and a greater thrombin-generating capacity in βERKO compared to WT mice. These results suggest that deficiencies in βER affect energy metabolism of platelets resulting in greater production of circulating thrombogenic microvesicles and could potentially explain increased predisposition to thromboembolism in some elderly females

Outer Membrane Vesicles Derived from Escherichia coli Induce Systemic Inflammatory Response Syndrome

Sepsis, characterized by a systemic inflammatory state that is usually related to Gram-negative bacterial infection, is a leading cause of death worldwide. Although the annual incidence of sepsis is still rising, the exact cause of Gram-negative bacteria-associated sepsis is not clear. Outer membrane vesicles (OMVs), constitutively secreted from Gram-negative bacteria, are nano-sized spherical bilayered proteolipids. Using a mouse model, we showed that intraperitoneal injection of OMVs derived from intestinal Escherichia coli induced lethality. Furthermore, OMVs induced host responses which resemble a clinically relevant condition like sepsis that was characterized by piloerection, eye exudates, hypothermia, tachypnea, leukopenia, disseminated intravascular coagulation, dysfunction of the lungs, hypotension, and systemic induction of tumor necrosis factor-α and interleukin-6. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of sepsis, suggesting OMVs as a new therapeutic target to prevent and/or treat severe sepsis caused by Gram-negative bacterial infection

Improving patient adherence to lifestyle advice (IMPALA): a cluster-randomised controlled trial on the implementation of a nurse-led intervention for cardiovascular risk management in primary care (protocol)

Background Many patients at high risk of cardiovascular diseases are managed and monitored in general practice. Recommendations for cardiovascular risk management, including lifestyle change, are clearly described in the Dutch national guideline. Although lifestyle interventions, such as advice on diet, physical exercise, smoking and alcohol, have moderate, but potentially relevant effects in these patients, adherence to lifestyle advice in general practice is not optimal. The IMPALA study intends to improve adherence to lifestyle advice by involving patients in decision making on cardiovascular prevention by nurse-led clinics. The aim of this paper is to describe the design and methods of a study to evaluate an intervention aimed at involving patients in cardiovascular risk management. Methods A cluster-randomised controlled trial in 20 general practices, 10 practices in the intervention arm and 10 in the control arm, starting on October 2005. A total of 720 patients without existing cardiovascular diseases but eligible for cardiovascular risk assessment will be recruited. In both arms, the general practitioners and nurses will be trained to apply the national guideline for cardiovascular risk management. Nurses in the intervention arm will receive an extended training in risk assessment, risk communication, the use of a decision aid and adapted motivational interviewing. This communication technique will be used to support the shared decision-making process about risk reduction. The intervention comprises 2 consultations and 1 follow-up telephone call. The nurses in the control arm will give usual care after the risk estimation, according to the national guideline. Primary outcome measures are self-reported adherence to lifestyle advice and drug treatment. Secondary outcome measures are the patients' perception of risk and their motivation to change their behaviour. The measurements will take place at baseline and after 12 and 52 weeks. Clinical endpoints will not be measured, but the absolute 10-year risk of cardiovascular events will be estimated for each patient from medical records at baseline and after 1 year. Discussion The combined use of risk communication, a decision aid and motivational interviewing to enhance patient involvement in decision making is an innovative aspect of the intervention. Trial registration Current Controlled Trials ISRCTN5155672

Exercise therapy and cognitive behavioural therapy to improve fatigue, daily activity performance and quality of life in Postpoliomyelitis Syndrome: the protocol of the FACTS-2-PPS trial

Contains fulltext : 88661.pdf (publisher's version ) (Open Access)BACKGROUND: Postpoliomyelitis Syndrome (PPS) is a complex of late onset neuromuscular symptoms with new or increased muscle weakness and muscle fatigability as key symptoms. Main clinical complaints are severe fatigue, deterioration in functional abilities and health related quality of life. Rehabilitation management is the mainstay of treatment. Two different therapeutic interventions may be prescribed (1) exercise therapy or (2) cognitive behavioural therapy (CBT). However, the evidence on the effectiveness of both interventions is limited. The primary aim of the FACTS-2-PPS trial is to study the efficacy of exercise therapy and CBT for reducing fatigue and improving activities and quality of life in patients with PPS. Additionally, the working mechanisms, patients' and therapists' expectations of and experiences with both interventions and cost-effectiveness will be evaluated. METHODS/DESIGN: A multi-centre, single-blinded, randomized controlled trial will be conducted. A sample of 81 severely fatigued patients with PPS will be recruited from 3 different university hospitals and their affiliate rehabilitation centres. Patients will be randomized to one of three groups i.e. (1) exercise therapy + usual care, (2) CBT + usual care, (3) usual care. At baseline, immediately post-intervention and at 3- and 6-months follow-up, fatigue, activities, quality of life and secondary outcomes will be assessed. Costs will be based on a cost questionnaire, and statistical analyses on GEE (generalized estimated equations). Analysis will also consider mechanisms of change during therapy. A responsive evaluation will be conducted to monitor the implementation process and to investigate the perspectives of patients and therapists on both interventions. DISCUSSION: A major strength of the FACTS-2-PPS study is the use of a mixed methods design in which a responsive and economic evaluation runs parallel to the trial. The results of this study will generate new evidence for the rehabilitation treatment of persons with PPS. TRIAL REGISTRATION: Dutch Trial Register NTR1371

Write, draw, show, and tell: a child-centred dual methodology to explore perceptions of out-of-school physical activity

Background Research to increase children’s physical activity and inform intervention design has, to date, largely underrepresented children’s voices. Further, research has been limited to singular qualitative methods that overlook children’s varied linguistic ability and interaction preference. The aim of this study was to use a novel combination of qualitative techniques to explore children’s current views, experiences and perceptions of out-of-school physical activity as well as offering formative opinion about future intervention design. Methods Write, draw, show and tell (WDST) groups were conducted with 35 children aged 10–11 years from 7 primary schools. Data were analysed through a deductive and inductive process, firstly using the Youth Physical Activity Promotion Model as a thematic framework, and then inductively to enable emergent themes to be further explored. Pen profiles were constructed representing key emergent themes. Results The WDST combination of qualitative techniques generated complimentary interconnected data which both confirmed and uncovered new insights into factors relevant to children’s out-of-school physical activity. Physical activity was most frequently associated with organised sports. Fun, enjoyment, competence, and physical activity provision were all important predictors of children’s out-of-school physical activity. Paradoxically, parents served as both significant enablers (i.e. encouragement) and barriers (i.e. restricting participation) to physical activity participation. Some of these key findings would have otherwise remained hidden when compared to more traditional singular methods based approaches. Conclusions Parents are in a unique position to promote health promoting behaviours serving as role models, physical activity gatekeepers and choice architects. Given the strong socialising effect parents have on children’s physical activity, family-based physical activity intervention may offer a promising alternative compared to traditional school-based approaches. Parents' qualitative input is important to supplement children’s voices and inform future family-based intervention design. The WDST method developed here is an inclusive, interactive and child-centred methodology which facilitates the exploration of a wide range of topics and enhances data credibility