Cardiovascular safety of febuxostat and allopurinol in patients with gout and cardiovascular comorbidities

Comprehensive safety evaluation of new drugs for noncardiac indications is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk such as gout. Febuxostat is a potent nonpurine selective inhibitor of xanthine oxidase approved for the treatment of gout. Long-term CV safety of febuxostat is being established in a randomized, allopurinol-controlled clinical study in patients with gout who have increased CV risk using an analytical approach that provides 90% power to meet a noninferiority margin of 1.3 for the hazard ratio (HR) (febuxostat relative to allopurinol). The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, and unstable angina requiring urgent coronary revascularization. Approximately 7,500 men and women with gout and CV disease are being recruited and will be followed up for up to 5 years postrandomization. The statistical plan for the trial uses a design that evaluates the HR of febuxostat to allopurinol based on the primary CV composite end point when there are a maximum of 624 CV events. Interim analyses will be conducted when approximately 25%, 50%, and 75% of events have occurred. At each analysis, if the upper 1-sided confidence limit of the HR is <1.3, the study will be stopped, and the noninferiority of febuxostat relative to allopurinol with regard to CV risk will be declared. The CARES trial will define the CV safety profile of febuxostat and allopurinol in gout patients at high risk for CV events.     

Assessment of safety of performing percutaneous coronary intervention after a recent episode of gastrointestinal bleeding

Background: Little literature exists on the risk of performing coronary intervention (PCI) on patients who have had recent gastrointestinal bleeding (GIB), although bleeding after PCI has been identified as a risk factor for long-term mortality. Methods: Patients within the Cleveland Clinic PCI database who had acute GIB within 30 days preceding PCI during the same hospitalization (n = 79) were retrospectively compared to those who had PCI without recent GIB (n = 10 979) for mortality and need for revascularization. Baseline characteristics, laboratory values, procedures, morbidities, and mortality were compared using chi-square test for categorical variables and using Wilcoxon rank sum test for continuous variables. Mortality data was obtained using Social Security Death Index and demonstrated using Kaplan–Meier method. Results: The GIB group had more prevalent history of peptic ulcer disease, GIB, gastrointestinal or liver disease (P < 0.0001), transient ischemic accident (P = 0.017), peripheral vascular disease (P = 0.0002), significant carotid artery occlusion (P = 0.023), and myocardial infarction (P < 0.0001). 47% of patients had upper GIB with 20% needing endoscopic intervention. This group had more anemia (P < 0.0001), heart failure (P = 0.0001), cardiogenic shock (10% versus 1.4%, P < 0.001), cardiac arrest (7.6% versus 1%, P < 0.001). GIB group had worse in-hospital mortality (P < 0.0001), long-term mortality (P < 0.001), and a 7.6% re-bleeding incidence. Conclusions: Overall, the patients who had GIB preceding PCI had higher in-hospital mortality and long-term mortality compared with those without GIB before PCI.     

Natural products against cancer: Review on phytochemicals from marine sources in preventing cancer

Marine natural products have as of now been acknowledged as the most important source of bioactive substances and drug leads. Marine flora and fauna, such as algae, bacteria, sponges, fungi, seaweeds, corals, diatoms, ascidian etc. are important resources from oceans, accounting for more than 90% of the total oceanic biomass. They are taxonomically different with huge productive and are pharmacologically active novel chemical signatures and bid a tremendous opportunity for discovery of new anti-cancer molecules. The water bodies a rich source of potent molecules which improve existence suitability and serve as chemical shield against microbes and little or huge creatures. These molecules have exhibited a range of biological properties antioxidant, antibacterial, antitumour etc. In spite of huge resources enriched with exciting chemicals, the marine floras and faunas are largely unexplored for their anticancer properties. In recent past, numerous marine anticancer compounds have been isolated, characterized, identified and are under trials for human use. In this write up we have tried to compile about marine-derived compounds anticancer biological activities of diverse flora and fauna and their underlying mechanisms and the generous raise in these compounds examined for malignant growth treatment in the course of the most recent quite a long while.     

Towards enhanced community genetic literacy among a minority ethnic community: a participatory action research project

BackgroundInfant mortality is a key public health outcome showing substantial socioeconomic and ethnic inequalities in the UK. The UK Pakistani population has an infant mortality rate of over nine per 1000 livebirths, more than twice that for the population as a whole. Increased risk is partly attributable to rare autosomal recessive genetic disorders linked to the practice of customary consanguineous marriage. WHO recommends community-level action to raise genetic literacy combined with enhanced genetics services. However, UK interventions are in their infancy, with varied local initiatives and no national response. A combination of a valued social practice affecting marginalised communities, complicated patterns of risk, and low professional awareness, makes this a complex and contentious issue. Indeed, some previous intervention has generated considerable backlash. This study in Sheffield, a northern English city, aimed to develop a community-level genetic literacy intervention that would be sensitive and responsive to local information needs.MethodsA participatory approach was used, drawing on a user-centred design and engaging local people as coresearchers. Two phases of insight gathering made use of group discussions, interviews, and participatory exercises to describe current understanding, gaps in knowledge, and trusted networks of communication. A series of testing-and-refinement cycles were then undertaken to coproduce a set of communication materials tailored to subgroups, with materials being tested for acceptability, appeal, and comprehension.FindingsSix local people were trained as coresearchers. Over 200 people participated in the insight and testing work. Information needs and preferred communication channels varied widely, confirming population heterogeneity and diverse perspectives to the issue. Despite some resistance, there was strong demand for information and willingness to discuss the topic. Conveying accurate and consistent information was challenging, as was meeting differing demands for detail within generic materials. Key areas of confusion and mistrust were addressed. Narrative, real life audio (for local radio) and video (for social media) were recommended and developed, supported by factual information in leaflet and website form, and contained links to religious resources plus genetics services.InterpretationDevelopment of appropriate community-level genetic literacy interventions can be achieved through participatory action research. Evaluative work is now needed to assess the effect on knowledge and service uptake.FundingGenetics Disorders UK funded the study. SS is a Senior Research Fellow funded by the National Institute for Health Research (NIHR) School for Public Health Research. Preparatory work was funded by NIHR Collaboration for Leadership in Applied Health Research & Care for South Yorkshire.     

Correction: Acridinedione as selective flouride ion chemosensor: a detailed spectroscopic and quantum mechanical investigation

Correction for ‘Acridinedione as selective flouride ion chemosensor: a detailed spectroscopic and quantum mechanical investigation’ by Nafees Iqbal et al., RSC Adv., 2018, 8, 1993–2003.

The authors regret that the interpretation of the fluorescence spectra of compound 7i published in the original article was incorrect. In the original article, it was reported that upon excitation at 380 nm, the fluorescence spectrum of compound 7i showed two emission bands at 450 nm and 770 nm (Fig. 5b of the original article). The signal at 770 nm (previously reported as an emission band), is instead a second order diffraction (an artefact of diffraction grating/spectrofluorometer monochromator), as revealed from the literature.^1,2 The authors thank a reader for highlighting this mistake.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.