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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

Summary 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

Fall Risk Factors in Mid-Age Women: The Australian Longitudinal Study on Women's Health

Introduction In contrast to older adults, little is known about risk factors for falls in adults aged 50–64 years, despite a high prevalence of falls in this age group. The aim was to identify risk factors for falls in mid-age women and explore how associations change with age. Methods Data were analyzed in 2016 from women aged 50–55 years in 2001 (born 1946–1951) in the Australian Longitudinal Study on Women's Health. The predictor variables were health-related factors (measured 2001, 2004, 2007, 2010) and the outcome was falls in the past 12 months (measured 2004, 2007, 2010, 2013). Prospective associations between predictor variables and falls measured 3 years later were analyzed using logistic regression with complete data for 4,629, 7,096, 5,911, and 5,774 participants. Results In surveys, 20.5% (2004), 30.7% (2007), 30.5% (2010), and 26.6% (2013) of women reported a fall in the previous 12 months. In the univariable models, most factors were associated with falls 3 years later. In the multivariable models, higher odds of falling were found for overweight and obese women compared with healthy weight women at all survey intervals (OR range, 1.15–1.43). Impaired vision (OR range, 1.25–1.35) and poor physical functioning (OR range, 1.24–1.66) were associated with falls at three survey intervals. Depression (OR range, 1.31–1.42), leaking urine (OR range, 1.25–1.49), stiff/painful joints (OR range, 1.26–1.62), severe tiredness (OR range, 1.29–1.49), osteoporosis (OR range, 1.25–1.52), and hormone replacement therapy (OR range, 0.69–0.79) were associated with falls at two survey intervals. There was no obvious age-related increase or decrease in the number of statistically significant associations. Conclusions Identified fall risk factors varied over time, highlighting that falling involves a complex interplay of risk factors in mid-age women

Alterations in the expression of leukemia inhibitory factor following exercise: comparisons between wild-type and mdx muscles

Background: Leukemia inhibitory factor (LIF) is a pleiotropic cytokine, belonging to the interleukin-6 family of cytokines, that has been suggested to have positive effects on myogenesis following injury and to minimise dystrophic pathology in mdx mice. Previous reports have suggested that Lif mRNA is up-regulated in the limb and diaphragm muscles of mdx mice, in human cases of dystrophy and acutely following exercise. This study examined expression of Lif mRNA in the quadriceps muscles of mdx and wild-type mice that were either sedentary or allowed to exercise voluntarily for two weeks

Obesity, abdominal obesity and Alzheimer disease

Background/Aims: Obesity has a strong association with vascular and metabolic diseases, which have been linked with Alzheimer disease (AD). While recent studies have reported an association between mid-life obesity and dementia, the role of later-life obesity is less clear. This study investigated the relation between AD, obesity and abdominal obesity at later-life in a case-control study. Methods: Participants were 50 consecutive patients with probable AD from memory disorders clinics in Launceston, Australia, and Bristol, England, and 75 cognitively normal controls. Height and weight [from which body mass index (BMI) was calculated] and hip and waist circumferences (from which waist-hip ratio was calculated) were measured. Participants were classified according to their BMI as: underweight (BMI 0.9 (men) or >0.8 (women). Results: AD was associated with obesity [OR 9.5, 95% CI 2.4-37.3, p = 0.001], underweight (OR 5.4, CI 0.9-33.7, p = 0.07) and abdominal obesity (OR 2.5, CI 1.1-5.7, p = 0.027) using logistic regression analyses adjusted for age, sex and location. The inclusion of metabolic risk factors in the model increased the ORs for obesity (OR 12.6, CI 2.8-56.5, p = 0.001) and underweight (OR 7.9, CI 1.0-66.3, p = 0.056). Conclusion: AD may be associated with obesity, underweight and abdominal obesity at later life. Larger prospective studies are required to investigate this further. Copyright © 2006 S. Karger AG

Doppler ultrasonography and single-fiber laser Doppler flowmetry for measurement of hind limb blood flow in anesthetized horses

OBJECTIVE: To use Doppler ultrasonography and single-fiber laser Doppler flowmetry (LDF) to evaluate blood flow in the dependent and nondependent hind limbs of anesthetized horses and to evaluate changes in femoral arterial blood flow and microvascular skeletal muscle perfusion in response to administration of phenylephrine hydrochloride or dobutamine hydrochloride. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized and positioned in left lateral recumbency. Doppler ultrasonography was used to measure velocity and volumetric flow in the femoral vessels. Single-fiber LDF was used to measure relative microvascular perfusion at a single site in the semimembranosus muscles. Phenylephrine or dobutamine was then administered to decrease or increase femoral arterial blood flow, and changes in blood flow and microvascular perfusion were recorded. RESULTS: Administration of phenylephrine resulted in significant decreases in femoral arterial and venous blood flows and cardiac output and significant increases in mean aortic blood pressure, systemic vascular resistance, and PCV. Administration of dobutamine resulted in significant increases in femoral arterial blood flow, mean aortic blood pressure, and PCV. Significant changes in microvascular perfusion were not detected. CONCLUSION AND CLINICAL RELEVANCE: Results suggest that Doppler ultrasonography and single-fiber LDF can be used to study blood flows in the hind limbs of anesthetized horses. However, further studies are required to determine why changes in femoral arterial blood flows were not associated with changes in microvascular perfusio

Men, masculinities and heart disease: a systematic review of the qualitative literature

The aim of this study was to synthesize qualitative data on men's experiences of coronary heart disease (CHD). The authors searched for qualitative papers published before January 2007 in MEDLINE, EMBASE, British Nursing Index, CINAHL, PsychINFO and Web of Knowledge and used thematic analysis to synthesize findings. They found 136 studies that collected data on men's experiences of CHD. Only 27 studies took a gendered approach and only two aimed to investigate men's gendered experiences of CHD. Many men drew on discourses associated with hegemonic masculinity (e.g. demonstrating stoicism through delaying seeking professional help) when talking about the implications of the disease for their identity, relationships and paid work. However, some accounts challenged this dominant discourse. The authors argue that a more nuanced understanding of hegemonic masculinity should take account of the production of gendered narratives in the interview context, given that men 'do' gender when they give the impression of 'not doing' health