Kidney replacement therapy:trends in incidence, treatment, and outcomes of myocardial infarction and stroke in a nationwide Scottish study

BACKGROUND AND AIMS: Patients with kidney failure have a higher risk of cardiovascular disease compared with the general population. Whilst temporal trends of myocardial infarction and stroke are declining in the general population, these have not been evaluated in patients with kidney failure. This study aimed to describe national trends in the incidence, treatment, and outcomes of myocardial infarction and stroke in patients with kidney failure (i.e. on dialysis or with a kidney transplant) over a 20-year period, stratified by age and sex.METHODS: In this retrospective national data linkage study, all patients with kidney failure in Scotland (UK) receiving kidney replacement therapy between January 1996 and December 2016 were linked to national hospitalization, prescribing, and death records. The primary outcomes were the incidence of myocardial infarction and stroke, and subsequent cardiovascular death. Generalized additive models were constructed to estimate age-standardized, sex-stratified incidence rates and trends in cardiovascular and all-cause death. RESULTS: Amongst 16 050 patients with kidney failure [52 (SD 15) years; 41.5% women], there were 1992 [66 (SD 12) years; 34.8% women] and 996 [65 (SD 13) years; 45.1% women] incident myocardial infarctions and strokes, respectively, between January 1996 and December 2016. During this period, the age-standardized incidence of myocardial infarction per 100 000 decreased in men {from 4376 [95% confidence interval (CI) 3998–4785] to 1835 (95% CI 1692–1988)} and women [from 3268 (95% CI 2982–3593) to 1369 (95% CI 1257–1491)]. Similarly, the age-standardized incidence of stroke per 100 000 also decreased in men [from 1978 (95% CI 1795–2175) to 799 (95% CI 729–875)] and women [from 2234 (95% CI 2031–2468) to 903 (95% CI 824–990)]. Compared with the general population, the incidence of myocardial infarction was four- to eight-fold higher in patients with kidney failure, whilst for stroke it was two- to four-fold higher. The use of evidence-based cardioprotective treatment increased over the study period, and the predicted probability of cardiovascular death within 1 year of myocardial infarction for a 66-year-old patient with kidney failure (mean age of the cohort) fell in men (76.6% to 38.6%) and women (76.8% to 38.8%), and also decreased in both sexes following stroke (men, from 63.5% to 41.4%; women, from 67.6% to 45.8%). CONCLUSIONS: The incidence of myocardial infarction and stroke has halved in patients with kidney failure over the past 20 years but remains significantly higher than in the general population. Despite improvements in treatment and outcomes, the prognosis of these patients following myocardial infarction and stroke remains poor

Kidney replacement therapy: trends in incidence, treatment, and outcomes of myocardial infarction and stroke in a nationwide Scottish study

BACKGROUND AND AIMS: Patients with kidney failure have a higher risk of cardiovascular disease compared with the general population. Whilst temporal trends of myocardial infarction and stroke are declining in the general population, these have not been evaluated in patients with kidney failure. This study aimed to describe national trends in the incidence, treatment, and outcomes of myocardial infarction and stroke in patients with kidney failure (i.e. on dialysis or with a kidney transplant) over a 20-year period, stratified by age and sex.METHODS: In this retrospective national data linkage study, all patients with kidney failure in Scotland (UK) receiving kidney replacement therapy between January 1996 and December 2016 were linked to national hospitalization, prescribing, and death records. The primary outcomes were the incidence of myocardial infarction and stroke, and subsequent cardiovascular death. Generalized additive models were constructed to estimate age-standardized, sex-stratified incidence rates and trends in cardiovascular and all-cause death.RESULTS: Amongst 16 050 patients with kidney failure [52 (SD 15) years; 41.5% women], there were 1992 [66 (SD 12) years; 34.8% women] and 996 [65 (SD 13) years; 45.1% women] incident myocardial infarctions and strokes, respectively, between January 1996 and December 2016. During this period, the age-standardized incidence of myocardial infarction per 100 000 decreased in men {from 4376 [95% confidence interval (CI) 3998-4785] to 1835 (95% CI 1692-1988)} and women [from 3268 (95% CI 2982-3593) to 1369 (95% CI 1257-1491)]. Similarly, the age-standardized incidence of stroke per 100 000 also decreased in men [from 1978 (95% CI 1795-2175) to 799 (95% CI 729-875)] and women [from 2234 (95% CI 2031-2468) to 903 (95% CI 824-990)]. Compared with the general population, the incidence of myocardial infarction was four- to eight-fold higher in patients with kidney failure, whilst for stroke it was two- to four-fold higher. The use of evidence-based cardioprotective treatment increased over the study period, and the predicted probability of cardiovascular death within 1 year of myocardial infarction for a 66-year-old patient with kidney failure (mean age of the cohort) fell in men (76.6% to 38.6%) and women (76.8% to 38.8%), and also decreased in both sexes following stroke (men, from 63.5% to 41.4%; women, from 67.6% to 45.8%).CONCLUSIONS: The incidence of myocardial infarction and stroke has halved in patients with kidney failure over the past 20 years but remains significantly higher than in the general population. Despite improvements in treatment and outcomes, the prognosis of these patients following myocardial infarction and stroke remains poor.</p

Kidney replacement therapy:trends in incidence, treatment, and outcomes of myocardial infarction and stroke in a nationwide Scottish study

BACKGROUND AND AIMS: Patients with kidney failure have a higher risk of cardiovascular disease compared with the general population. Whilst temporal trends of myocardial infarction and stroke are declining in the general population, these have not been evaluated in patients with kidney failure. This study aimed to describe national trends in the incidence, treatment, and outcomes of myocardial infarction and stroke in patients with kidney failure (i.e. on dialysis or with a kidney transplant) over a 20-year period, stratified by age and sex.METHODS: In this retrospective national data linkage study, all patients with kidney failure in Scotland (UK) receiving kidney replacement therapy between January 1996 and December 2016 were linked to national hospitalization, prescribing, and death records. The primary outcomes were the incidence of myocardial infarction and stroke, and subsequent cardiovascular death. Generalized additive models were constructed to estimate age-standardized, sex-stratified incidence rates and trends in cardiovascular and all-cause death. RESULTS: Amongst 16 050 patients with kidney failure [52 (SD 15) years; 41.5% women], there were 1992 [66 (SD 12) years; 34.8% women] and 996 [65 (SD 13) years; 45.1% women] incident myocardial infarctions and strokes, respectively, between January 1996 and December 2016. During this period, the age-standardized incidence of myocardial infarction per 100 000 decreased in men {from 4376 [95% confidence interval (CI) 3998–4785] to 1835 (95% CI 1692–1988)} and women [from 3268 (95% CI 2982–3593) to 1369 (95% CI 1257–1491)]. Similarly, the age-standardized incidence of stroke per 100 000 also decreased in men [from 1978 (95% CI 1795–2175) to 799 (95% CI 729–875)] and women [from 2234 (95% CI 2031–2468) to 903 (95% CI 824–990)]. Compared with the general population, the incidence of myocardial infarction was four- to eight-fold higher in patients with kidney failure, whilst for stroke it was two- to four-fold higher. The use of evidence-based cardioprotective treatment increased over the study period, and the predicted probability of cardiovascular death within 1 year of myocardial infarction for a 66-year-old patient with kidney failure (mean age of the cohort) fell in men (76.6% to 38.6%) and women (76.8% to 38.8%), and also decreased in both sexes following stroke (men, from 63.5% to 41.4%; women, from 67.6% to 45.8%). CONCLUSIONS: The incidence of myocardial infarction and stroke has halved in patients with kidney failure over the past 20 years but remains significantly higher than in the general population. Despite improvements in treatment and outcomes, the prognosis of these patients following myocardial infarction and stroke remains poor

Pharmacological profile of the sodium current in human stem cell-derived cardiomyocytes compares to heterologous Nav1.5+β1 model

The cardiac Nav1.5 mediated sodium current (I-Na) generates the upstroke of the action potential in atrial and ventricular myocytes. Drugs that modulate this current can therefore be antiarrhythmic or proarrhythmic, which requires preclinical evaluation of their potential drug-induced inhibition or modulation of Nav1.5. Since Nav1.5 assembles with, and is modulated by, the auxiliary beta 1-subunit, this subunit can also affect the channel's pharmacological response. To investigate this, the effect of known Nav1.5 inhibitors was compared between COS-7 cells expressing Nav1.5 or Nav1.5+beta 1 using whole-cell voltage clamp experiments. For the open state class Ia blockers ajmaline and quinidine, and class Ic drug flecainide, the affinity did not differ between both models. For class Ib drugs phenytoin and lidocaine, which are inactivated state blockers, the affinity decreased more than a twofold when beta 1 was present. Thus, beta 1 did not influence the affinity for the class Ia and Ic compounds but it did so for the class Ib drugs. Human stem cell-derived cardiomyocytes (hSC-CMs) are a promising translational cell source for in vitro models that express a representative repertoire of channels and auxiliary proteins, including beta 1. Therefore, we subsequently evaluated the same drugs for their response on the I-Na in hSC-CMs. Consequently, it was expected and confirmed that the drug response of I-Na in hSC-CMs compares best to I-Na expressed by Nav1.5+beta 1

The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells

Human-induced pluripotent stem cell (hiPSC) and stem cell (hSC) derived cardiomyocytes (CM) are gaining popularity as in vitro model for cardiology and pharmacology studies. A remaining flaw of these cells, as shown by single-cell electrophysiological characterization, is a more depolarized resting membrane potential (RMP) compared to native CM. Most reports attribute this to a lower expression of the Kir2.1 potassium channel that generates the I-K1 current. However, most RMP recordings are obtained from isolated hSC/hiPSC-CMs whereas in a more native setting these cells are interconnected with neighboring cells by connexin-based gap junctions, forming a syncytium. Hereby, these cells are electrically connected and the total pool of I-K1 increases. Therefore, the input resistance (Ri) of interconnected cells is lower than that of isolated cells. During patch clamp experiments pipettes need to be well attached or sealed to the cell, which is reflected in the seal resistance (Rs), because a nonspecific ionic current can leak through this pipette-cell contact or seal and balance out small currents within the cell such as I-K1. By recording the action potential of isolated hSC-CMs and that of hSC-CMs cultured in small monolayers, we show that the RMP of hSC-CMs in monolayer is approximately -20 mV more hyperpolarized compared to isolated cells. Accordingly, adding carbenoxolone, a connexin channel blocker, isolates the cell that is patch clamped from its neighboring cells of the monolayer and depolarizes the RMP. The presented data show that the recorded RMP of hSC-CMs in a syncytium is more negative than that determined from isolated hSC/hiPSC-CMs, most likely because the active pool of Kir2.1 channels increased

Psychosocial impact of the summer 2007 floods in England

Background The summer of 2007 was the wettest in the UK since records began in 1914 and resulted in severe flooding in several regions. We carried out a health impact assessment using population-based surveys to assess the prevalence of and risk factors for the psychosocial consequences of this flooding in the United Kingdom. Methods Surveys were conducted in two regions using postal, online, telephone questionnaires and face-to-face interviews. Exposure variables included the presence of flood water in the home, evacuation and disruption to essential services (incident management variables), perceived impact of the floods on finances, house values and perceived health concerns. Validated tools were used to assess psychosocial outcome (mental health symptoms): psychological distress (GHQ-12), anxiety (GAD-7), depression (PHQ-9) and probable post-traumatic stress disorder (PTSD checklist-shortform). Multivariable logistic regression was used to describe the association between water level in the home, psychological exposure variables and incident management variables, and each mental health symptom, adjusted for age, sex, presence of an existing medical condition, employment status, area and data collection method. Results The prevalence of all mental health symptoms was two to five-fold higher among individuals affected by flood water in the home. People who perceived negative impact on finances were more likely to report psychological distress (OR 2.5, 1.8-3.4), probable anxiety (OR 1.8, 1.3-2.7) probable depression (OR 2.0, 1.3-2.9) and probable PTSD (OR 3.2, 2.0-5.2). Disruption to essential services increased adverse psychological outcomes by two to three-fold. Evacuation was associated with some increase in psychological distress but not significantly for the other three measures. Conclusion The psychosocial and mental health impact of flooding is a growing public health concern and improved strategies for minimising disruption to essential services and financial worries need to be built in to emergency preparedness and response systems. Public Health Agencies should address the underlying predictors of adverse psychosocial and mental health when providing information and advice to people who are or are likely to be affected by flooding

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

Simulation Study of Photon-to-Digital Converter (PDC) Timing Specifications for LoLX Experiment

The Light only Liquid Xenon (LoLX) experiment is a prototype detector aimed to study liquid xenon (LXe) light properties and various photodetection technologies. LoLX is also aimed to quantify LXe's time resolution as a potential scintillator for 10~ps time-of-flight (TOF) PET. Another key goal of LoLX is to perform a time-based separation of Cerenkov and scintillation photons for new background rejection methods in LXe experiments. To achieve this separation, LoLX is set to be equipped with photon-to-digital converters (PDCs), a photosensor type that provides a timestamp for each observed photon. To guide the PDC design, we explore requirements for time-based Cerenkov separation. We use a PDC simulator, whose input is the light information from the Geant4-based LoLX simulation model, and evaluate the separation quality against time-to-digital converter (TDC) parameters. Simulation results with TDC parameters offer possible configurations supporting a good separation. Compared with the current filter-based approach, simulations show Cerenkov separation level increases from 54% to 71% when using PDC and time-based separation. With the current photon time profile of LoLX simulation, the results also show 71% separation is achievable with just 4 TDCs per PDC. These simulation results will lead to a specification guide for the PDC as well as expected results to compare against future PDC-based experimental measurements. In the longer term, the overall LoLX results will assist large LXe-based experiments and motivate the assembly of a LXe-based TOF-PET demonstrator system.Comment: 5 pages, 7 figure