Febuxostat in the management of hyperuricemia and chronic gout: a review

Febuxostat is a novel, potent, non-purine selective xanthine oxidase inhibitor, which in clinical trials demonstrated superior ability to lower and maintain serum urate levels below 6 mg/dL compared with conventionally used doses of allopurinol. Febuxostat was well tolerated in long term treatment in patients with hyperuricemia including those experiencing hypersensitity/intolerance to allopurinol. Dose adjustment appears unnecessary in patients with mild to moderate renal or liver insufficiency or advanced age. The most common adverse reactions reported were abnormal liver function tests, headache, and gastrointestinal symptoms, which were usually mild and transient. However, whether hepatotoxicity becomes a limitation in the use of febuxostat needs to be determined in further studies. An increased frequency of gout flares occurs for a prolonged period after treatment initiation, as with any aggressive lowering of serum urate, and prolonged prophylaxis with colchicine or NSAIDs is usually required. Febuxostat has been granted marketing authorization by the European Commission in early 2008 for the treatment of chronic hyperuricemia and gout. Febuxostat is the first major treatment alternative for gout in more than 40 years and is a promising alternative to allopurinol, although continued long-term surveillance on safety and efficacy is required

Benzobisoxazole cruciforms: a tunable, cross-conjugated platform for the generation of deep blue OLED materials

Four new cross-conjugated small molecules based on a central benzo[1,2-d:4,5-d′]bisoxazole moiety possessing semi-independently tunable HOMO and LUMO levels were synthesized and the properties of these materials were evaluated experimentally and theoretically. The molecules were thermally stable with 5% weight loss occurring well above 350 °C. The cruciforms all exhibited blue emission in solution ranging from 433–450 nm. Host–guest OLEDs fabricated from various concentrations of these materials using the small molecule host 4,4′-bis(9-carbazolyl)-biphenyl (CBP) exhibited deep blue-emission with Commission Internationale de L'Eclairage (CIE) coordinates of (0.15 ≤ x ≤ 0.17, 0.05 ≤ y ≤ 0.11), and maximum luminance efficiencies as high as ∼2 cd A−1. These results demonstrate the potential of benzobisoxazole cruciforms as emitters for developing high-performance deep blue OLEDs.We would like to thank Dr Sarah Cady, Dr Kamel Harrata and Mr Steven Veysey of Iowa State University (ISU) Chemical Instrumentation Facility for compound analysis. We thank Eeshita Manna for technical assistance. We also thank the National Science Foundation (CHE-1413173) for financial support of this work. RK and JS were partially supported by Basic Energy Sciences, Division of Materials Science and Engineering, USDOE. Ames Laboratory is operated by Iowa State University for the US Department of Energy (USDOE) under Contract No. DE-AC 02-07CH11358. Computational resources were provided in part by the MERCURY consortium (http://mercuryconsortium.org/) under NSF grants CHE-0116435, CHE-0521063, CHE-0849677, and CHE-1229354. (CHE-1413173 - National Science Foundation; Basic Energy Sciences, Division of Materials Science and Engineering, USDOE; DE-AC 02-07CH11358 - Iowa State University for the US Department of Energy (USDOE); CHE-0116435 - MERCURY consortium under NSF; CHE-0521063 - MERCURY consortium under NSF; CHE-0849677 - MERCURY consortium under NSF; CHE-1229354 - MERCURY consortium under NSF)http://pubs.rsc.org/en/Content/ArticleLanding/2016/TC/C5TC03622D#!divAbstractPublished versio

Effects of Some Common Food Constituents on Cardiovascular Disease

Cardiovascular diseases are the major cause of morbidity and mortality worldwide, and there is considerable interest in the role of dietary constituents and supplements in the prevention and treatment of these disorders. We reviewed the major publications related to potential effects on cardiovascular risk factors and outcomes of some common dietary constituents: carotenoids, flavonoid-rich cocoa, tea, red wine and grapes, coffee, omega-3 fatty acids, and garlic. Increased intake of some of these has been associated with reduced all-cause mortality or reduced incidence of myocardial infraction, stroke, and hypertension. However, although the evidence from observational studies is supportive of beneficial effects for most of these foodstuffs taken as part of the diet, potential benefits from the use of supplements derived from these natural products remain largely inconclusive

Systematic Review and Meta-Analysis of Statin Use and Mortality, Intensive Care Unit Admission and Requirement for Mechanical Ventilation in COVID-19 Patients

There is mounting evidence that statin use is beneficial for COVID-19 outcomes. We performed a systematic review and meta-analysis to evaluate the association between statin use and mortality, intensive care unit (ICU) admission and mechanical ventilation in COVID-19 patients, on studies which provided covariate adjusted effect estimates, or performed propensity score matching. We searched PubMed, Embase, Web of Science and Scopus for studies and extracted odds or hazard ratios for specified outcome measures. Data synthesis was performed using a random-effects inverse variance method. Risk of bias, heterogeneity and publication bias were analyzed using standard methods. Our results show that statin use was associated with significant reductions in mortality (OR = 0.72, 95% CI: 0.67–0.77; HR = 0.74, 95% CI: 0.69, 0.79), ICU admission (OR = 0.94, 95% CI: 0.89–0.99; HR = 0.76, 95% CI: 0.60–0.96) and mechanical ventilation (OR = 0.84, 95% CI: 0.78–0.92; HR = 0.67, 95% CI: 0.47–0.97). Nevertheless, current retrospective studies are based on the antecedent use of statins prior to infection and/or continued use of statin after hospital admission. The results may not apply to the de novo commencement of statin treatment after developing COVID-19 infection. Prospective studies are lacking and necessary

Study of the Effects of Total Flavonoids of Astragalus on Atherosclerosis Formation and Potential Mechanisms

Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P < 0.05 to 0.01), increased HDL cholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile

809-1 Different Respiratory Rates Affect the Measurement of Autonomic Tone by Power Spectral Analysis of Heart Rate Variability in Patients with Heart Failure

Power spectral analysis of heart rate variability is frequently used as an easy non invasive method for assessing autonomic tone. However changes in respiratory rate are frequently ignored and these may have an important effect on the measurements of spectral components, especially in heart failure. We have assessed the effect of different respiratory rates (10, 15, 20 min-1 and spontaneous) on low frequency (LF) and high frequency (HF) components of HR variability in 11 heart failure pts (CCF) (EF=40±4%; 9 males) and 9 normal subjects (5 males).ResultsLF &amp; HF spectral power in normalized units (%); S=spontaneous (mean±SEM)LF10HF10LF15HF15LF20HF20LFSHFSSupineCCF19±863±9*18±554±713±447±8*16±649± 8Normal14±668±818±658±1015±670±522±955±10StandCCF15±766±619±746±830±1051±97±531±10Normal28±955±830±942±958±1027±550±1217±5*p&lt;0.05Supine HF power falls with increasing respiratory rate in most CCF pts and this effect is similar to that seen in normals on standing (i.e. at increased sympathetic levels). An improvement in clinical state of CCF pts will lower respiratory rate and this effect alone will increase HF power rather than any therapy

Using a mHealth system to recall and refer existing clients and refer community members with health concerns to primary healthcare facilities in South Africa: a feasibility study

Background: Lay health workers (LHWs) are critical in linking communities and primary healthcare (PHC) facilities. Effective communication between facilities and LHWs is key to this role. We implemented a mobile health (mHealth) system to improve communication and continuity of care for chronically ill clients. The system focused on requests from facility staff to LHWs to follow up clients and LHW referrals of people who needed care at a facility. We implemented the system in two rural and semi-rural sub-districts in South Africa. Objective: To assess the feasibility of the mHealth system in improving continuity of care for clients in PHC in South Africa. Method: We implemented the intervention in 15 PHC facilities. The clerks issued recalls to LHWs using a tablet computer. LHWs used smartphones to receive these requests, communicate with clerks and refer people to a facility. We undertook a mixed-methods evaluation to assess the feasibility of the mHealth system. We analysed recall and referral data using descriptive statistics. We used thematic content analysis to analyse qualitative data from semi-structured interviews with facility staff and a researcher fieldwork journal. Results: Across the sub-districts, 2,204 clients were recalled and 628 (28%) of these recalls were successful. LHWs made 1,085 referrals of which 485 (45%) were successful. The main client group referred and recalled were children under 5 years. Qualitative data showed the impacts of facility conditions and interpersonal relationships on the mHealth system. Conclusion: Using mHealth for recalls and referrals is probably feasible and can improve communication between LHWs and facility staff. However, the low success rates highlight the need to assess facility capacity beforehand and to integrate mHealth with existing health information systems. mHealth may improve communication between LHWs and facility staff, but its success depends on the health system capacity to incorporate these interventions