A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve.

AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).ConclusionsIn this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.Trial registrationclinicaltrials.gov Identifier: NCT01342029

Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies

BACKGROUND: Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut. METHODS: Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, r(s), between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age. RESULTS: There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, r(s )= 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, r(s )= 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, r(s )= 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, r(s )= 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: r(s )= 0.360 (n = 46, P = 0.014). CONCLUSION: Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species

Access to electronic health records by care setting and provider type: perceptions of cancer care providers in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>The use of electronic health records (EHRs) to support the organization and delivery of healthcare is evolving rapidly. However, little is known regarding potential variation in access to EHRs by provider type or care setting. This paper reports on observed variation in the perceptions of access to EHRs by a wide range of cancer care providers covering diverse cancer care settings in Ontario, Canada.</p> <p>Methods</p> <p>Perspectives were sought regarding EHR access and health record completeness for cancer patients as part of an internet survey of 5663 cancer care providers and administrators in Ontario. Data were analyzed using a multilevel logistic regression model. Provider type, location of work, and access to computer or internet were included as covariates in the model.</p> <p>Results</p> <p>A total of 1997 of 5663 (35%) valid responses were collected. Focusing on data from cancer care providers (N = 1247), significant variation in EHR access and health record completeness was observed between provider types, location of work, and level of computer access. Providers who worked in community hospitals were half as likely as those who worked in teaching hospitals to have access to their patients' EHRs (OR 0.45 95% CI: 0.24–0.85, p < 0.05) and were six times less likely to have access to other organizations' EHRs (OR 0.15 95% CI: 0.02–1.00, p < 0.05). Compared to surgeons, nurses (OR 3.47 95% CI: 1.80–6.68, p < 0.05), radiation therapists/physicists (OR 7.86 95% CI: 2.54–25.34, p < 0.05), and other clinicians (OR 4.92 95% CI: 2.15–11.27, p < 0.05) were more likely to report good access to their organization's EHRs.</p> <p>Conclusion</p> <p>Variability in access across different provider groups, organization types, and geographic locations illustrates the fragmented nature of EHR adoption in the cancer system. Along with focusing on technological aspects of EHR adoption within organizations, it is essential that there is cross-organizational and cross-provider access to EHRs to ensure patient continuity of care, system efficiency, and high quality care.</p

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

Developing and testing a nurse-led intervention to support bereavement in relatives in the intensive care (BRIC study): a protocol of a pre-post intervention study

BACKGROUND: When a patient is approaching death in the intensive care unit (ICU), patients' relatives must make a rapid transition from focusing on their beloved one's recovery to preparation for their unavoidable death. Bereaved relatives may develop complicated grief as a consequence of this burdensome situation; however, little is known about appropriate options in quality care supporting bereaved relatives and the prevalence and predictors of complicated grief in bereaved relatives of deceased ICU patients in the Net

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology