Emergency Department (ED) attendances with chest pain reduced during the COVID-19 lockdown. We performed a service evaluation project in NHS Lothian to explore how and why the COVID-19 pandemic and ...public health advice had affected chest pain presentations and help-seeking behaviour at an individual patient level using a qualitative interview approach.
We carried out 28 semi-structured telephone interviews with a convenience sample of patients who presented with chest pain during lockdown and in patients with known coronary heart disease under the outpatient care of a cardiologist in April and May 2020. Interviews were audio recorded and voice files listened to while making detailed notes. Salient themes and issues were documented as verbatim extracts. Interviews were analysed thematically.
Patient interviews revealed three main themes. 1) pandemic help-seeking behaviour; describing how participants made the decision to seek professional healthcare assessment. 2) COVID-19 exposure concerns; describing how the subthemes of perceived vulnerability, wishing to protect others and adding pressure to the health service shaped their decision making for an episode of acute chest pain. 3) hospital experience; describing the difference between the imagined and actual experience in hospital.
Qualitative interviews revealed how the pandemic shaped help-seeking practices, how patients interpreted their personal vulnerability to the virus, and described patient experience of attending hospital for assessment during this time. As patient numbers presenting to hospital appeared to mirror public health messaging, dynamic monitoring of this messaging should evaluate public response to healthcare campaigns to ensure the net impact on health, pandemic and non-pandemic related, is optimised.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiomyocytes proliferate profusely during early development and for a brief period after birth in mammals. Within a month after birth, this proliferative capability is dramatically reduced in ...mammals unlike lower vertebrates where it persists into adult life. The zebrafish, for example, retains the ability to regenerate the apex of the heart following resection by a mechanism predominantly driven by cardiomyocyte proliferation. Differences in proliferative capacity of cardiomyocytes in adulthood between mammals and lower vertebrates are closely liked to ontogenetic or phylogenetic factors. Elucidation of these factors has the potential to provide enormous benefits if they lead to the development of therapeutic strategies that facilitate cardiomyocyte proliferation. In this review, we highlight the differences between Mammalian and Zebrafish cardiomyocytes, which could explain at least in part the different proliferative capacities in these two species. We discuss the advantages of the zebrafish as a model of cardiomyocyte proliferation, particularly at the embryonic stage. We also identify a number of key molecular pathways with potential to reveal key steps in switching cardiomyocytes from a quiescent to a proliferative phenotype.
BACKGROUNDPatients with advanced heart failure have substantial supportive care needs. Specialist palliative care can be beneficial, but it is unclear who is most appropriate for referral and when ...patients should be referred.OBJECTIVESWe conducted a Delphi study of international experts to identify consensus referral criteria for specialist palliative care for patients with advanced heart failure.METHODSClinicians from 5 continents with expertise in the integration of cardiology and palliative care were asked to rate 34 disease-based, 24 needs-based, and 9 time-based criteria over 3 rounds. Consensus was defined a priori as ≥70% agreement. A criterion was coded as major if the experts endorsed that meeting that criterion alone was adequate to justify a referral.RESULTSThe response rate was 44 of 46 (96%), 41 of 46 (89%), and 43 of 46 (93%) in the first, second, and third rounds, respectively. Panelists reached consensus on 25 major criteria for specialist palliative care referral. The 25 major criteria were categorized under 6 topics, including "advanced/refractory heart failure, comorbidities, and complications" (eg, cardiac cachexia, cardiorenal syndrome) (n = 8), "advanced heart failure therapies" (eg, chronic inotropes, precardiac transplant) (n = 4), "hospital utilization" (eg, emergency room visits, hospitalization) (n = 2), "prognostic estimate" (n = 1), "symptom burden/distress" (eg, severe physical/emotional/spiritual distress) (n = 6), and "decision making/social support" (eg, goals-of-care discussions) (n = 4). The majority (68%) of major criteria had ≥90% agreement.CONCLUSIONSInternational experts reached consensus on a large number of criteria for referral to specialist palliative care. With further validation, these criteria may be useful for standardizing palliative care access in the inpatient and/or outpatient settings.
Studies in global androgen receptor knockout (G-ARKO) and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation ...used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall.
Mice with selective deletion of AR (ARKO) from vascular smooth muscle cells (SM-ARKO), endothelial cells (VE-ARKO), or both (SM/VE-ARKO) were compared with wild type (WT) controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO) did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture) model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10(-10)-10(-7)M; 6 days).
These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clinical endpoint adjudication Meah, Mohammed N; Denvir, Martin A; Mills, Nicholas L ...
The Lancet (British edition),
06/2020, Letnik:
395, Številka:
10240
Journal Article
Recenzirano
Odprti dostop
In pivotal clinical effectiveness trials, the primary endpoint needs to be precisely defined and quantified because any misclassification could introduce noise and possible bias, potentially leading ...to incorrect trial conclusions. The underlying premise is that adjudication will be more accurate, reduce noise, and limit any misclassification by the site investigator, with any residual errors being consistently distributed across the treatment groups. Some observers have been critical of the absence of endpoint adjudication in trials using these data and point to inaccuracies of hospital coding and statistics.25 In systems where payment to the health care service is reliant on coding data, external factors such as reimbursement incentives or local practice variations can cause bias.26 In large international trials, a further concern is the heterogeneity and reporting biases of different health care systems. ...subsequent follow up for over 20 years has now been done entirely through routinely collected data.34,35 Similar findings have also been found in the more contemporary aspirin for primary prevention in people with diabetes mellitus (ASCEND) trial,36,37 where hospital episode statistics in England, UK were compared with adjudicated clinical endpoints and effect size estimates for the primary outcome were again very similar (personal communication, Jane Armitage, University of Oxford).
Three-dimensional fluorescence time-lapse imaging of the beating heart is extremely challenging, due to the heart's constant motion and a need to avoid pharmacological or phototoxic damage. Although ...real-time triggered imaging can computationally "freeze" the heart for 3D imaging, no previous algorithm has been able to maintain phase-lock across developmental timescales. We report a new algorithm capable of maintaining day-long phase-lock, permitting routine acquisition of synchronised 3D + time video time-lapse datasets of the beating zebrafish heart. This approach has enabled us for the first time to directly observe detailed developmental and cellular processes in the beating heart, revealing the dynamics of the immune response to injury and witnessing intriguing proliferative events that challenge the established literature on cardiac trabeculation. Our approach opens up exciting new opportunities for direct time-lapse imaging studies over a 24-hour time course, to understand the cellular mechanisms underlying cardiac development, repair and regeneration.
Risk prediction after myocardial infarction is often complex in older patients. The Global Registry of Acute Coronary Events (GRACE) model includes clinical parameters and age, but not frailty. We ...hypothesised that frailty would enhance the prognostic properties of GRACE.
We performed a prospective observational cohort study in two independent cardiology units: the Royal Infirmary of Edinburgh, UK (primary cohort) and the South Yorkshire Cardiothoracic Centre, Sheffield, UK (external validation). The study sample included 198 patients ≥65 years old hospitalised with type 1 myocardial infarction (primary cohort) and 96 patients ≥65 years old undergoing cardiac catheterisation for myocardial infarction (external validation). Frailty was assessed using the Clinical Frailty Scale (CFS). The GRACE 2.0 estimated risk of 12-month mortality, Charlson comorbidity index and Karnofsky disability scale were also determined for each patient.
Forty (20%) patients were frail (CFS ≥5). These individuals had greater comorbidity, functional impairment and a higher risk of death at 12 months (49% vs. 9% in non-frail patients, p < 0.001). The hazard of 12-month all-cause mortality nearly doubled per point increase in CFS after adjustment for age, sex and comorbidity (Hazard Ratio HR 1.90, 95% CI 1.47-2.44, p < 0.001). The CFS had good discrimination for mortality by Receiver Operating Characteristic (ROC) curve analysis (Area Under the Curve AUC 0.81, 95% CI 0.72-0.89) and enhanced the GRACE estimate (AUC 0.86 vs. 0.80 without CFS, p = 0.04). At existing GRACE thresholds, the CFS resulted in a Net Reclassification Improvement (NRI) of 0.44 (95% CI 0.28-0.60, p < 0.001), largely through reductions in risk estimates amongst non-frail patients. Similar findings were observed in the external validation cohort (NRI 0.46, 95% CI 0.23-0.69, p < 0.001).
The GRACE score overestimated mortality risk after myocardial infarction in these cohorts of older patients. The CFS is a simple guided frailty tool that may enhance prediction in this setting. These findings merit evaluation in larger cohorts of unselected patients.
Clinicaltrials.gov; NCT02302014 (November 26th 2014, retrospectively registered).
A network of molecular factors drives the development, differentiation, and maintenance of endothelial cells. Friend leukemia integration 1 transcription factor (FLI1) is a bona fide marker of ...endothelial cells during early development. In zebrafish
, we identified two endothelial cell populations, high-
and low-
, by the intensity of green fluorescent protein signal. By comparing RNA-sequencing analysis of non-
expressing cells (
) with these two (
) cell populations, we identified several up-regulated genes, not previously recognized as important, during endothelial development. Compared with
and low-
cells, high-
cells showed up-regulated expression of the zinc finger transcription factor PRDI-BF1 and RIZ homology domain containing 16 (
).
knockdown (KD) by morpholino in the zebrafish larva was associated with impaired angiogenesis and increased number of low-
cells at the expense of high-
cells. In addition,
KD in endothelial cells derived from human-induced pluripotent stem cells impaired their differentiation and migration in vitro. Moreover, zebrafish mutants (mut) with loss of function for the oncogene LIM domain only 2 (
) also showed reduced
gene expression combined with impaired angiogenesis.
expression was reduced further in endothelial (CD31
) cells compared with CD31
cells isolated from
-mutants (
mut) embryos. Chromatin immunoprecipitation-PCR demonstrated that Lmo2 binds to the promoter and directly regulates the transcription of
This work unveils a mechanism by which
expression is activated in endothelial cells by Lmo2 and highlights a possible therapeutic pathway by which to modulate endothelial cell growth and repair.
Despite the importance of nitric oxide signaling in multiple biological processes, its role in tissue regeneration remains largely unexplored. Here, we provide evidence that inducible nitric oxide ...synthase (iNos) translocates to the nucleus during zebrafish tailfin regeneration and is associated with alterations in the nuclear S-nitrosylated proteome. iNos inhibitors or nitric oxide scavengers reduce protein S-nitrosylation and impair tailfin regeneration. Liquid chromatography/tandem mass spectrometry reveals an increase of up to 11-fold in the number of S-nitrosylated proteins during regeneration. Among these, Kdm1a, a well-known epigenetic modifier, is S-nitrosylated on Cys334. This alters Kdm1a binding to the CoRest complex, thus impairing its H3K4 demethylase activity, which is a response specific to the endothelial compartment. Rescue experiments show S-nitrosylation is essential for tailfin regeneration, and we identify downstream endothelial targets of Kdm1a S-nitrosylation. In this work, we define S-nitrosylation as an essential post-translational modification in tissue regeneration.
AbstractObjectiveTo evaluate how selection of patients for high sensitivity cardiac troponin testing affects the diagnosis of myocardial infarction across different healthcare ...settings.DesignProspective study of three independent consecutive patient populations presenting to emergency departments.SettingSecondary and tertiary care hospitals in the United Kingdom and United States.ParticipantsHigh sensitivity cardiac troponin I concentrations were measured in 8500 consecutive patients presenting to emergency departments: unselected patients in the UK (n=1054) and two selected populations of patients in whom troponin testing was requested by the attending clinician in the UK (n=5815) and the US (n=1631). The final diagnosis of type 1 or type 2 myocardial infarction or myocardial injury was independently adjudicated.Main outcome measuresPositive predictive value of an elevated cardiac troponin concentration for a diagnosis of type 1 myocardial infarction.ResultsCardiac troponin concentrations were elevated in 13.7% (144/1054) of unselected patients, with a prevalence of 1.6% (17/1054) for type 1 myocardial infarction and a positive predictive value of 11.8% (95% confidence interval 7.0% to 18.2%). In selected patients, in whom troponin testing was guided by the attending clinician, the prevalence and positive predictive value were 14.5% (843/5815) and 59.7% (57.0% to 62.2%) in the UK and 4.2% (68/1631) and 16.4% (13.0% to 20.3%) in the US. Across both selected patient populations, the positive predictive value was highest in patients with chest pain, with ischaemia on the electrocardiogram, and with a history of ischaemic heart disease.ConclusionsWhen high sensitivity cardiac troponin testing is performed widely or without previous clinical assessment, elevated troponin concentrations are common and predominantly reflect myocardial injury rather than myocardial infarction. These observations highlight how selection of patients for cardiac troponin testing varies across healthcare settings and markedly influences the positive predictive value for a diagnosis of myocardial infarction.
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