Thromboprophylaxis in atrial fibrillation and association with cognitive decline: systematic review

Objective:Atrial Fibrillation (AF) is associated with dementia. If AF-related cognitive decline is driven by cerebral embolic events, thromboprophylaxis may impact on this. This systematic review assessed the association between cognitive impairment and AF thromboprophylaxis. Methods:Two independent reviewers searched CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science Core Collection, and Cochrane Library from inception until 12th November 2014. Eligible studies compared AF thromboprophylaxis to control with an outcome measure of cognition or dementia. Where data allowed, meta-analyses describing between-group differences in cognitive test scores or rates of incident dementia were performed. Results:Nineteen studies were eligible. For two prospective studies (one RCT) comparing anticoagulation against antiplatelet therapy, change in Mini-Mental State Examination score from baseline to last follow-up (maximal duration:5.9 years) suggested a difference favouring anticoagulation (mean difference:0.90, 95% CI:0.29 to 1.51), in keeping with a trend seen in the single RCT (mean difference MMSE:0.80. 95% CI:-0.07 to 1.67). Pooled odds ratios suggested no association with incident dementia, comparing anticoagulant to antiplatelet therapy (two studies, OR:1.23, 95% CI:0.80 to 1.91) or no treatment (three studies, OR:0.89, 95%CI:0.47 to 1.69). Conclusions:Our analyses show no definitive evidence of cognitive benefit or harm from anticoagulation. We demonstrated a potential benefit of anticoagulation in comparison to antiplatelet over time. Larger-scale studies with longer follow-up are needed to determine the true cognitive impact of AF thromboprophylaxis

Mid-IR Luminosities and UV/Optical Star Formation Rates at z<1.4

UV continuum and mid-IR emission constitute two widely used star formation indicators at intermediate and high redshifts. We study 2430 galaxies with z<1.4 in the Extended Groth Strip with MIPS 24 mic observations from FIDEL, spectroscopy from DEEP2, and UV, optical, and near-IR photometry from AEGIS. The data are coupled with stellar population models and Bayesian SED fitting to estimate dust-corrected SFRs. In order to probe the dust heating from stellar populations of various ages, the derived SFRs were averaged over various timescales--from 100 Myr for "current" SFR to 1--3 Gyr for long-timescale SFRs. These SED-based UV/optical SFRs are compared to total infrared luminosities extrapolated from 24 mic observations. We find that for the blue, actively star forming galaxies the correlation between the IR luminosity and the UV/optical SFR shows a decrease in scatter when going from shorter to longer SFR-averaging timescales. We interpret this as the greater role of intermediate age stellar populations in heating the dust than what is typically assumed. This holds over the entire redshift range. Many so-called green valley galaxies are simply dust-obscured actively star-forming galaxies. However, there exist 24 mic-detected galaxies, some with L>10^11 L_sun, yet with little current star formation. For them a reasonable amount of dust absorption of stellar light is sufficient to produce the observed levels of IR. In our sample optical and X-ray AGNs do not contribute on average more than ~50% to the mid-IR luminosity, and we see no evidence for a large population of "IR excess" galaxies (Abridged).Comment: Accepted for publication in ApJ. Content identical to arXiv version 1. No color figure

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Using line acceleration to measure false killer whale (Pseudorca crassidens) click and whistle source levels during pelagic longline depredation

False killer whales (Pseudorca crassidens) depredate pelagic longlines in offshore Hawaiian waters. On January 28, 2015 a depredation event was recorded 14m from an integrated GoPro camera, hydrophone, and accelerometer, revealing that false killer whales depredate bait and generate clicks and whistles under good visibility conditions. The act of plucking bait off a hook generated a distinctive 15 Hz line vibration. Two similar line vibrations detected at earlier times permitted the animal’s range and thus signal source levels to be estimated over a 25-min window. Peak power spectral density source levels for whistles (4–8 kHz) were estimated to be between 115 and 130 dB re 1 lPa2/Hz @ 1 m. Echolocation click source levels over 17–32 kHz bandwidth reached 205 dB re 1lPa @ 1 m pk-pk, or 190 dB re 1lPa @ 1 m (root-meansquare). Predicted detection ranges of the most intense whistles are 10 to 25 km at respective sea states of 4 and 1, with click detection ranges being 5 times smaller than whistles. These detection range analyses provide insight into how passive acoustic monitoring might be used to both quantify and avoid depredation encounters.The authors are indebted to Captain Jerry Ray and the rest of the F/V Katy Mary crew for permitting the camera gear to be deployed during their longline fishing trip. Robert Glatts designed the custom GoPro circuit board, and Will Cerf assisted with video footage analysis. This research was sponsored by Derek Orner under the Bycatch Reduction Engineering Program (BREP) at the National Oceanic and Atmospheric Administration (NOAA).Ye

Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients

<p>Abstract</p> <p>Background</p> <p>HIV-1-infected elite controllers or suppressors (ES) maintain undetectable viral loads (< 50 copies/mL) without antiretroviral therapy. The mechanisms of suppression are incompletely understood. Modulation of HIV-1 replication by miRNAs has been reported, but the role of small RNAs in ES is unknown. Using samples from a well-characterized ES cohort, untreated viremic patients, and uninfected controls, we explored the PBMC miRNA profile and probed the relationships of miRNA expression, CD4+ T-cell counts, and viral load.</p> <p>Results</p> <p>miRNA profiles, obtained using multiple acquisition, data processing, and analysis methods, distinguished ES and uninfected controls from viremic HIV-1-infected patients. For several miRNAs, however, ES and viremic patients shared similar expression patterns. Differentially expressed miRNAs included those with reported roles in HIV-1 latency (miR-29 family members, miRs -125b and -150). Others, such as miR-31 and miR-31*, had no previously reported connection with HIV-1 infection but were found here to differ significantly with uncontrolled HIV-1 replication. Correlations of miRNA expression with CD4+ T-cell count and viral load were found, and we observed that ES with low CD4+ T-cell counts had miRNA profiles more closely related to viremic patients than controls. However, expression patterns indicate that miRNA variability cannot be explained solely by CD4+ T-cell variation.</p> <p>Conclusions</p> <p>The intimate involvement of miRNAs in disease processes is underscored by connections of miRNA expression with the HIV disease clinical parameters of CD4 count and plasma viral load. However, miRNA profile changes are not explained completely by these variables. Significant declines of miRs-125b and -150, among others, in both ES and viremic patients indicate the persistence of host miRNA responses or ongoing effects of infection despite viral suppression by ES. We found no negative correlations with viral load in viremic patients, not even those that have been reported to silence HIV-1 in vitro, suggesting that the effects of these miRNAs are exerted in a focused, cell-type-specific manner. Finally, the observation that some ES with low CD4 counts were consistently related to viremic patients suggests that miRNAs may serve as biomarkers for risk of disease progression even in the presence of viral suppression.</p

Baseline factors associated with early and late death in intracerebral haemorrhage survivors

Background and purpose: The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors. Methods: This was a secondary analysis of the multicentre prospective observational CROMIS‐2 ICH study. Death was defined as ‘early’ if occurring within 6 months of study entry and ‘late’ if occurring after this time point. Results: In our cohort (n = 1094), there were 306 deaths (per 100 patient‐years: absolute event rate, 11.7; 95% confidence intervals, 10.5–13.1); 156 were ‘early’ and 150 ‘late’. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre‐event modified Rankin scale score (per point increase; HR, 1.41, P &lt; 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P &lt; 0.0001) and haemorrhage volume &gt;60 mL (HR, 4.08, P &lt; 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre‐event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time. Conclusions: We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH

Characterisation of age and polarity at onset in bipolar disorder

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses