Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions

Small vessel disease encompasses lacunar stroke, white matter hyperintensities, lacunes and microbleeds. It causes a quarter of all ischemic strokes, is the commonest cause of vascular dementia, and the cause is incompletely understood. Vascular prophylaxis, as appropriate for large artery disease and cardioembolism, includes antithrombotics, and blood pressure and lipid lowering; however, these strategies may not be effective for small vessel disease, or are already used routinely so precluding further detailed study. Further, intensive antiplatelet therapy is known to be hazardous in small vessel disease through enhanced bleeding. Whether acetylcholinesterase inhibitors, which delay the progression of Alzheimer's dementia, are relevant in small vessel disease remains unclear. Potential prophylactic and treatment strategies might be those that target brain microvascular endothelium and the blood brain barrier, microvascular function and neuroinflammation. Potential interventions include endothelin antagonists, neurotrophins, nitric oxide donors and phosphodiesterase 5 inhibitors, peroxisome proliferator-activated receptor-gamma agonists, and prostacyclin mimics and phosphodiesterase 3 inhibitors. Several drugs that have relevant properties are licensed for other disorders, offering the possibility of drug repurposing. Others are in development. Since influencing multiple targets may be most effective, using multiple agents and/or those that have multiple effects may be preferable. We focus on potential small vessel disease mechanistic targets, summarize drugs that have relevant actions, and review data available from randomized trials on their actions and on the available evidence for their use in lacunar stroke

On the Correlated X-ray and Optical Evolution of SS Cygni

We have analyzed the variability and spectral evolution of the prototype dwarf nova system SS Cygni using RXTE data and AAVSO observations. A series of pointed RXTE/PCA observations allow us to trace the evolution of the X-ray spectrum of SS Cygni in unprecedented detail, while 6 years of optical AAVSO and RXTE/ASM light curves show long-term patterns. Employing a technique in which we stack the X-ray flux over multiple outbursts, phased according to the optical light curve, we investigate the outburst morphology. We find that the 3-12 keV X-ray flux is suppressed during optical outbursts, a behavior seen previously, but only in a handful of cycles. The several outbursts of SS Cygni observed with the more sensitive RXTE/PCA also show a depression of the X-rays during optical outburst. We quantify the time lags between the optical and X-ray outbursts, and the timescales of the X-ray recovery from outburst. The optical light curve of SS Cygni exhibits brief anomalous outbursts. During these events the hard X-rays and optical flux increase together. The long-term data suggest that the X-rays decline between outburst. Our results are in general agreement with modified disk instability models (DIM), which invoke a two-component accretion flow consisting of a cool optically thick accretion disk truncated at an inner radius, and a quasi-spherical hot corona-like flow extending to the surface of the white dwarf. We discuss our results in the framework of one such model, involving the evaporation of the inner part of the optically thick accretion disk, proposed by Meyer & Meyer-Hofmeister (1994).Comment: 24 pages, 8 figures, 2 tables, accepted for publication in Ap

The Stationary Phase Method for a Wave Packet in a Semiconductor Layered System. The applicability of the method

Using the formal analysis made by Bohm in his book, {\em "Quantum theory"}, Dover Publications Inc. New York (1979), to calculate approximately the phase time for a transmitted and the reflected wave packets through a potential barrier, we calculate the phase time for a semiconductor system formed by different mesoscopic layers. The transmitted and the reflected wave packets are analyzed and the applicability of this procedure, based on the stationary phase of a wave packet, is considered in different conditions. For the applicability of the stationary phase method an expression is obtained in the case of the transmitted wave depending only on the derivatives of the phase, up to third order. This condition indicates whether the parameters of the system allow to define the wave packet by its leading term. The case of a multiple barrier systems is shown as an illustration of the results. This formalism includes the use of the Transfer Matrix to describe the central stratum, whether it is formed by one layer (the single barrier case), or two barriers and an inner well (the DBRT system), but one can assume that this stratum can be comprise of any number or any kind of semiconductor layers.Comment: 15 pages, 4 figures although figure 4 has 5 graph

Dipyridamole plus aspirin versus aspirin alone in the secondary prevention after TIA or stroke: a meta-analysis by risk

Objectives: Our aim was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D. Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on the comparison of A+D versus ASA were excluded. Review methods: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification. Results: A total of 7,612 patients (5 trials) were included in the analyses, 3,800 allocated to A+D and 3,812 to ASA alone. The trial-adjusted hazard ratio for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval 0.72-0.92). Hazard ratios did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke, HR 0.78 (95% CI 0.68 – 0.90). Conclusion: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischemic stroke of presumed arterial origin in the secondary prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk. ---------------------------7dc3521430776 Content-Disposition: form-data; name="c14_creators_1_name_family" Halke

Statistical analysis of the primary outcome in acute stroke trials

Common outcome scales in acute stroke trials are ordered categorical or pseudocontinuous in structure but most have been analyzed as binary measures. The use of fixed dichotomous analysis of ordered categorical outcomes after stroke (such as the modified Rankin Scale) is rarely the most statistically efficient approach and usually requires a larger sample size to demonstrate efficacy than other approaches. Preferred statistical approaches include sliding dichotomous, ordinal, or continuous analyses. Because there is no best approach that will work for all acute stroke trials, it is vital that studies are designed with a full understanding of the type of patients to be enrolled (in particular their case mix, which will be critically dependent on their age and severity), the potential mechanism by which the intervention works (ie, will it tend to move all patients somewhat, or some patients a lot, and is a common hazard present), a realistic assessment of the likely effect size, and therefore the necessary sample size, and an understanding of what the intervention will cost if implemented in clinical practice. If these approaches are followed, then the risk of missing useful treatment effects for acute stroke will diminish

Quality of life among adults following bariatric and body contouring surgery: a systematic review.

Background: Weight loss following bariatric surgery is associated with significant improvements in obesity-related comorbidities, body satisfaction and psychosocial outcomes, at least in the short term. However, in the context of extreme weight loss, body image and appearance may worsen again because the “excess” or “loose” skin can lead to both functional and profound dissatisfaction with appearance. These concerns have led to an increasing uptake of post-bariatric surgery, “body-contouring” procedures but the implications for quality of life (QoL) have not been thoroughly considered. Objective/purpose: The objective was to identify the best available evidence regarding the QoL outcomes for adults following bariatric and body contouring surgery. Inclusion criteria Types of participants: The review considered studies involving people aged 18 years and beyond who underwent bariatric surgery and body contouring surgery. Types of interventions: The review considered studies that evaluated bariatric surgery as well as body contouring surgery. Types of studies: The review considered both experimental and epidemiological study designs. Outcomes: The primary outcomes were QoL as measured by validated tools at less than two years, two to five years and more than five years following body contouring surgery. The secondary outcomes were adverse events, unsatisfactory aesthetic appearance and weight gain. Search strategy: Six databases were searched, including Cochrane Central, MEDLINE, Embase, Web of Science, PsycINFO and CINAHL. Studies published from 1954 to 2014 were considered. Additional searches for unpublished studies were undertaken in BIOSIS citation index, Register of Current Controlled Trials and Global Health Observatory. Methodological quality: The methodological quality of eligible studies was assessed independently by two reviewers using the Joanna Briggs Institute quality assessment tool. Data extraction: Data extraction from the included studies was undertaken and summarized independently by two reviewers using the standardized Joanna Briggs Institute data extraction tool. Data synthesis: Studies were too heterogeneous and could not be pooled in statistical meta-analysis. Therefore, the data results are presented as a narrative summary in relation to the outcomes of interest. Results: Nine quantitative studies (four comparable cohort studies, including two group design and two four-group designs and five descriptive or case-series studies) were included in the review. The included studies reported significant clinical improvements in appearance, wellbeing and QoL. These included primary outcomes pointing to body image satisfaction, improved self-esteem and confidence, improved physical function/pain and improved social function. The secondary outcomes were related to adverse events in the early postoperative period and reported wound healing problems, including seromas, partial necrosis, dehiscence, hematoma and anemia because of blood loss. Also, some data sets shed light on appearance-related distress and body dysphoria post surgery associated with visible scars and contour deformities. Conclusion: Body contouring surgery has been shown to have positive benefits, especially in relation to improved wellbeing, function and QoL. However, adjustment to changing body image following body contouring is both challenging and empowering and seems to be a transitional process

The pattern of penetration and aspiration in acute stroke survivors

Background and Aims: Aspiration is common in acute stroke survivors with dysphagia, is associated with increased pneumonia rates, and is an independent predictor of mortality. However, studies evaluating the nature and pattern of penetration and aspiration post-stroke are lacking. Method: The Penetration-Aspiration Scale (PAS) was used to rate baseline videofluoroscopic swallowing studies of 17 dysphagic stroke survivors from the STEPS trial of pharyngeal electrical stimulation (onset <14 days, mean 74 years). Analysis was performed on 6 x 5ml boli and 1 x 50ml bolus (thin fluids with contrast agent at 40% wt/vol), recorded at 25 f/s. Every swallow to clear each 5ml or 50ml bolus was counted, given a PAS score and labelled a primary or secondary (clearing) swallow. Results: In total, 285 swallows were viewed. Due to poor image quality, 7% of swallows were excluded. At a bolus level, for 5ml/50ml swallows, results showed 68%/42% normal swallows, 14%/27% penetration and 18%/31% aspiration respectively. At a subject level, 5ml: only 3 patients scored within normal limits for all boli; 50ml: no subject swallowed without showing penetration or aspiration at some point. Higher penetration and aspiration scores occurred on 50ml. Aspirated material was rarely fully cleared, even in those subjects who demonstrated a cough response (5ml: 2%, 50 ml: 0%). Conclusion: Aspiration in post-stroke dysphagia appears to fluctuate in presentation within and between boli. Bedside assessments should take into account variability and sample enough swallows. In addition, clinicians should not assume coughing clears aspirated material. Quality of image capture must be optimised for future studies

Synthetic NLTE accretion disc spectra for the dwarf nova SS Cyg during an outburst cycle

Dwarf nova outbursts result from enhanced mass transport through the accretion disc of a cataclysmic variable system. We assess the question of whether these outbursts are caused by an enhanced mass transfer from the late-type main sequence star onto the white dwarf (so-called mass transfer instability model, MTI) or by a thermal instability in the accretion disc (disc instability model, DIM). We compute non-LTE models and spectra of accretion discs in quiescence and outburst and construct spectral time sequences for discs over a complete outburst cycle. We then compare our spectra to published optical spectroscopy of the dwarf nova SS Cygni. In particular, we investigate the hydrogen and helium line profiles that are turning from emission into absorption during the rise to outburst. The evolution of the hydrogen and helium line profiles during the rise to outburst and decline clearly favour the disc-instability model. Our spectral model sequences allow us to distinguish inside-out and outside-in moving heating waves in the disc of SS Cygni, which can be related to symmetric and asymmetric outburst light curves, respectively.Comment: 8 pages, 8 figures; accepted to A&

ORFEUS II and IUE Spectroscopy of EX Hydrae

Using ORFEUS-SPAS II FUV spectra, IUE UV spectra, and archival EUVE deep survey photometry, we present a detailed picture of the behavior of the magnetic cataclysmic variable EX Hydrae. Like HUT spectra of this source, the FUV and UV spectra reveal broad emission lines of He II, C II-IV, N III and V, O VI, Si III-IV, and Al III superposed on a continuum which is blue in the UV and nearly flat in the FUV. Like ORFEUS spectra of AM Her, the O VI doublet is resolved into broad and narrow emission components. Consistent with its behavior in the optical, the FUV and UV continuum flux densities, the FUV and UV broad emission line fluxes, and the radial velocity of the O VI broad emission component all vary on the spin phase of the white dwarf, with the maximum of the FUV and UV continuum and broad emission line flux light curves coincident with maximum blueshift of the broad O VI emission component. On the binary phase, the broad dip in the EUV light curve is accompanied by strong eclipses of the UV emission lines and by variations in both the flux and radial velocity of the O VI narrow emission component. The available data are consistent with the accretion funnel being the source of the FUV and UV continuum and the O VI broad emission component, and the white dwarf being the source of the O VI narrow emission component.Comment: 21 pages, 10 Postscript figures; LaTeX format, uses aaspp4.sty; table2.tex included separately because it must be printed sideways - see instructions in the file; accepted on 1999 Feb 20 for publication in The Astrophysical Journa

Understanding the lived experiences of Mexican informal caregivers with Ambient Assisted Living Technologies

Ambient Assisted Living (AAL) Technologies, have the potential to support the people with dementia living in their homes for longer. Dementia is a major public health concern. It currently affects approximately 46.8 million people worldwide and by 2050 this figure will increase to 131.5 million. Low-and-middle income countries (LMIC) will be particularly affected by this situation as their poor health infrastructures and governmental support will mean that they have to rely on the informal caregiver (IC) sector. ICs are people who care for a dependent or disabled family member, commonly spouses or daughters. Mexico was the first Spanish speaking country in the world to recognise dementia as a public health priority. In-home technologies, such as AAL Technologies, are used in dementia care in order to improve patients’ and caregivers’ quality of life. This paper explores the way in which Mexican ICs of people with dementia (PWD) make sense of their lived experiences with AAL technologies