Do clinically relevant differences in outcomes exist between women and men undergoing treatment for cardiovascular disease?

IntroductionThroughout my own clinical practice, I became aware that differences may exist between men and women in the decisions for treatment and the outcomes after intervention for cardiovascular disease. Clinical trials have corroborated this with women typically presenting at an older age and studies have suggested there are innate differences between the sexes with women believed to have worse outcomes than men. However, historically women have been poorly represented in clinical trials, which has led to biased result interpretation, despite cardiovascular disease remaining the leading cause of death in women. Therefore, extrapolation of results to women may lead to differences in expected outcomes.The aim of this thesis was to explore the question: ‘Do outcomes differ between women and men in the treatment of cardiovascular disease?’MethodsThe over-arching research question was addressed by integrating results from 5 individual datasets. Following the literature review, the areas identified for investigation were: 1) The role of female sex in the treatment of the left main coronary artery; 2) Bleeding risk in women undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction; 3) Does sex play a role in the activated clotting time during angioplasty; 4) The role of sex on outcomes following transcatheter aortic valve implantation; and 5) Sex differences in the perceived intensity of symptoms in patients with aortic stenosis.Each of these studies involved observational data from real world patients and allowed for assessment of matched populations to allow for a comparison when appropriate. The datasets were then analysed utilising the constructivist paradigm to identify themes that contribute to robust and generalisable new knowledge in this field.ResultsThe treatment of the complex left main coronary artery is first addressed and demonstrates no differences between the sexes in those undergoing percutaneous coronary intervention, however there was an advantage in women undergoing coronary artery bypass grafting. In patients presenting with ST-elevation myocardial infarction, women have more episodes of bleeding, however despite this have the same good outcome as men in hospital and therefore require the same access to treatment. The anti-coagulation regime during percutaneous coronary intervention is then considered and demonstrates that for a similar dose of unfractionated heparin, women are more likely to have a very high activated clotting time which may explain the increased risk of bleeding in the prior chapter.In the assessment of aortic stenosis, in symptomatic patients undergoing transcatheter aortic valve implantation, women again appear to have an advantage over men, with male sex a predictor of mortality at long-term follow-up. However, finally addressing the symptomatology of aortic stenosis, there were no differences between sexes in the symptoms of breathlessness or in NT-pro-BNP levels.ConclusionsThe analysis demonstrated that despite an older presentation in women who underwent treatment, women can do as well as men (in coronary artery disease) or even fare better (for transcatheter aortic valve implantation) despite more bleeding and vascular complications. This may impact significantly regarding the multi-disciplinary discussion regarding intervention for these patients and needs to be considered by the clinicians involved in the treatment of cardiovascular disease.The limitations of the studies are that the data are non-randomised and in 2 of the data sets there are small sample sizes. Additionally, there are the difficulties associated with the analysis of mixed methods research in analysing quantitative data qualitatively.In summary, when determining if patient sex should be a factor when deciding upon the management of acquired cardiovascular disease, the triangulation of data from across a number of data sets in this thesis suggests that sex should not be the primary consideration. Further research is needed to refine clinical understanding of which factors should be taken into account

Stent Thrombosis: Incidence, Predictors and New Technologies

Some concerns have been raised regarding the risk of late and very late stent thrombosis (ST) following drug-eluting stent implantation. Despite remaining an uncommon complication of percutaneous coronary intervention, when ST occurs, it can be catastrophic to the individual, commonly presenting as acute ST elevation myocardial infarction or sudden cardiac death. The incidence and predictors of ST have been reported in the literature and the role of dual antiplatelet therapies in the avoidance of such a complication remains vital. Ongoing studies are assessing the role of these therapies including platelet reactivity testing, genetic testing and optimum duration of therapy. In addition, newer polymer-free and bioabsorbable stents are under investigation in the quest to potentially minimise the risk of ST

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 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

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

The psychological science accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data