Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16,

A Characterization and Cell Toxicity Assessment of Particulate Pollutants from Road Traffic Sites in Kano State, Nigeria

Emerging African countries are characterized by explosive population growth and urbanization, which threaten environmental sustainability. This study comparatively characterized ambient aerosols and assessed cytotoxicity to facilitate improving health and environmental policy. Twenty-four air samples were collected at high and low-density traffic sites in Kano State using polysulfone and stainless steel filters attached to an automated pump. The physico-chemical properties of particulate matter were determined using scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX). In vitro, their potential toxicity was assessed using macrophages and cell fixation with staining. Results showed 51.7% of particles as PM2.5, with the highest particle concentration in mixed sites (urban and industrial). Particle classification into four groups by elemental composition and structure showed: sand particles (Si, Al, Fe, Ca, Mg, K, Na, Mo, Sr, Zr) 30–51%; other fibers 0–3%; other particles (Si, Fe, S, Mo, Zn, and other metals) 22–40%; and silicone-based fibres 23–34%. The abundant elements are: Si, Al, Ca, Ce, Ti, Fe, Cl, Pb, and Mn. The lowest viability on cytotoxicity assessment was recorded in mixed site M2. The majority of households were located within 50 m of air sampling sites. Proximity to traffic sites worsens health, as evidenced in cytotoxicity findings. We recommend improved urban planning and intensification of emissions control

Annual research review: harms experienced by child users of online and mobile technologies: the nature, prevalence and management of sexual and aggressive risks in the digital age

Aims and scope: The usage of mobile phones and the internet by young people has increased rapidly in the past decade, approaching saturation by middle childhood in developed countries. Besides many benefits, online content, contact or conduct can be associated with risk of harm; most research has examined whether aggressive or sexual harms result from this. We examine the nature and prevalence of such risks, and evaluate the evidence regarding the factors that increase or protect against harm resulting from such risks, so as to inform the academic and practitioner knowledge base. We also identify the conceptual and methodological challenges encountered in this relatively new body of research, and highlight the pressing research gaps. Methods: Given the pace of change in the market for communication technologies, we review research published since 2008. Following a thorough bibliographic search of literature from the key disciplines (psychology, sociology, education, media studies and computing sciences), the review concentrates on recent, high quality empirical studies, contextualizing these within an overview of the field. Findings: Risks of cyberbullying, contact with strangers, sexual messaging (‘sexting’) and pornography generally affect fewer than one in five adolescents. Prevalence estimates vary according to definition and measurement, but do not appear to be rising substantially with increasing access to mobile and online technologies, possibly because these technologies pose no additional risk to offline behaviour, or because any risks are offset by a commensurate growth in safety awareness and initiatives. While not all online risks result in self-reported harm, a range of adverse emotional and psychosocial consequences is revealed by longitudinal studies. Useful for identifying which children are more vulnerable than others, evidence reveals several risk factors: personality factors (sensation-seeking, low self-esteem, psychological difficulties), social factors (lack of parental support, peer norms) and digital factors (online practices, digital skills, specific online sites). Conclusions: Mobile and online risks are increasingly intertwined with pre-existing (offline) risks in children's lives. Research gaps, as well as implications for practitioners, are identified. The challenge is now to examine the relations among different risks, and to build on the risk and protective factors identified to design effective interventions