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Background and Purpose: Atrial fibrillation and heart failure with reduced ejection fraction (HFrEF) are common sources of cardioembolism. While oral anticoagulation is strongly recommended for atrial fibrillation, there are marked variations in guideline recommendations for HFrEF due to uncertainty about net clinical benefit. This systematic review and meta-analysis evaluates the comparative association of oral anticoagulation with stroke and other cardiovascular risk in populations with atrial fibrillation or HFrEF in sinus rhythm and identify factors mediating different estimates of net clinical benefit. Methods: PubMed and Embase were searched from database inception to November 20, 2019 for randomized clinical trials comparing oral anticoagulation to control. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall and within atrial fibrillation and HFrEF trials. Differences in treatment effect were assessed by estimating I 2 among all trials and testing the between-trial-population P -interaction. The primary outcome measure was all stroke. Secondary outcome measures were ischemic stroke, hemorrhagic stroke, mortality, myocardial infarction, and major hemorrhage. Results: Twenty-one trials were eligible for inclusion, 15 (n=19 332) in atrial fibrillation (mean follow-up: 23.1 months), and 6 (n=9866) in HFrEF (mean follow-up: 23.9 months). There were differences in primary outcomes between trial populations, with all-cause mortality included for 95.2% of HFrEF trial population versus 0.38% for atrial fibrillation. Mortality was higher in controls groups of HFrEF populations (19.0% versus 9.6%) but rates of stroke lower (3.1% versus 7.0%) compared with atrial fibrillation. The association of oral anticoagulation with all stroke was consistent for atrial fibrillation (odds ratio, 0.51 [95% CI, 0.42–0.63]) and HFrEF (odds ratio, 0.61 [95% CI, 0.47–0.79]; I 2 =12.4%; P interaction=0.31). There were no statistically significant differences in the association of oral anticoagulation with cardiovascular events, mortality or bleeding between populations. Conclusions: The relative association of oral anticoagulation with stroke risk, and other cardiovascular outcomes, is similar for patients with atrial fibrillation and HFrEF. Differences in the primary outcomes employed by trials in HFrEF, compared with atrial fibrillation, may have contributed to differing conclusions of the relative efficacy of oral anticoagulation.

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas.

Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status—wealth and education—differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. Findings Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96–1·58) for high-income countries, 1·59 (1·42–1·78) in middle-income countries, and 2·23 (1·79–2·77) in low-income countries (pinteractionInterpretation Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

BackgroundAdaptive design methods are intended to improve efficiency of clinical trials and are relevant to evaluating interventions in dialysis populations. We sought to quantify the use of adaptive designs in dialysis clinical trials.MethodsWe completed a full text systematic review and adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Our review utilised a machine learning classifier and a novel full text systematic review method. We searched MEDLINE (Pubmed) and performed a detailed data extraction of trial characteristics and a completed a narrative synthesis of the data.Results50 studies, available as 66 articles, were included after full text review. 31 studies were conducted in a dialysis population and 19 studies had renal replacement therapy as a primary or secondary outcome. While the absolute number of adaptive design methods is increasing over time, the relative use of adaptive design methods in dialysis trials is decreasing over time (6.1% in 2009 to 0.3% in 2019). Adaptive design methods impacted 52% of dialysis trials they were used in. Group sequential designs were the most common type of adaptive design method used. Acute Kidney Injury (AKI) was studied in 27 trails (54%), End Stage Kidney Disease (ESKD) was studied in 22 trials (44%) and Chronic Kidney Disease (CKD) was studied in 1 trial (2%). 26 studies (52%) were supported by public funding. 41 studies (82%) did not report their adaptive design method in the title or abstract and would not be detected by a standard systematic.ConclusionsAdaptive design methods are employed in dialysis trials, but there has been a decline in their relative use over time.Registration NumberPROSPERO: CRD42020163946Significance statementWhat was previously known about the specific topic of the manuscript?The use of adaptive designs methods in dialysis trials is unquantified.What were the most important findings? If studies are animals, this should be specifiedAlthough absolute numbers of adaptive design trials have increased over time, the proportion of dialysis trials using an adaptive design has reduced. Among trials that employed an adaptive design, 52% of dialysis trials were revised due to the adaptive criteria. Group sequential designs were the most common type of adaptive design method used in dialysis randomized clinical trials. Acute Kidney Injury (AKI) was studied in 54% of trials and End Stage Kidney Disease (ESKD) was studied in 44% of trials, which used an adaptive design.How does the new information advance a new understanding of the kidney and its diseases?Adaptive design methods are effective in dialysis trials, but their relative use has declined over time.

Introduction This study aimed to determine the prevalence of diabetic kidney disease (DKD) and rapid renal function decline and to identify indices associated with this decline among adults attending a diabetes center in Northern Europe. Research design and methods This is a retrospective cohort study of 4606 patients who attended a diabetes center in Ireland between June 2012 and December 2016. Definition/staging of chronic kidney disease used the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification based on data from the most recently attended appointment. Relevant longitudinal trends and variabilities were derived from serial records prior to index visit. Rapid renal function decline was defined based on per cent and absolute rates of estimated glomerular filtration rate (eGFR) change. Multiple linear regression was used to explore the relationships between explanatory variables and per cent eGFR change. Results 42.0% (total), 23.4% (type 1 diabetes), 47.9% (type 2 diabetes) and 32.6% (other diabetes) had DKD. Rapid decline based on per cent change was more frequent in type 2 than in type 1 diabetes (32.8% vs 14.0%, p

Digital, Objective Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. Methods We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. Results Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (pheterogeneity, Ciencias Médicas y de la Salud

IntroductionAdaptive design methods are a potential solution to improve efficiency of clinical trials but their uptake in dialysis is unknown. We aim to investigate the use of adaptive design methods in dialysis clinical trials and to cultivate further adoption of adaptive design methods by the nephrology community.Methods and analysisWe will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and the Cochrane Collaboration Handbook. We will perform a literature search through MEDLINE (PubMed), EMBASE and CENTRAL, a detailed data extraction of trial characteristics and a narrative synthesis of the data. There will be no language restrictions. We will estimate the percentage of adaptive clinical trials per year in dialysis. Subgroup analysis will be performed by dialysis modality, funder and geographical location.Ethics and disseminationEthical approval will not be required for this study as data will be obtained from publicly available clinical trials. We will disseminate our results in a peer-reviewed publication.PROSPERO registration number

Aims The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. Methods Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. Results The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. Conclusions This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.

Background: While low sodium intake ( Methods: This is a protocol for two phase IIb randomised, two-group, parallel, open-label, controlled, single centre trials. Participants were aged >40 years with stable blood pressure, unchanged anti-hypertensive medications, willing to modify diet and provided written informed consent. Participants were excluded for abnormal sodium handling, heart failure, high dose diuretics, immunosuppression, pregnancy/lactation, postural hypotension, cognitive impairment, high or low body mass index (BMI) or inclusion in another trial. STICK participants had estimated glomerular filtration rate (eGFR) 30-60ml/min/1.73m2 and were excluded for acute kidney Injury, rapidly declining eGFR; known glomerular disease or current use of non-steroidal anti-inflammatory drugs. For COSIP, participants were excluded for known kidney or cardiovascular disease. Participants were randomized to usual care only (healthy eating) or an additional sodium lowering intervention (target Discussion: These Phase II trials will explore uncertainty about low sodium intake and cardiovascular and kidney biomarkers, and help determine the feasibility of low sodium intake. Trial results will also provide preliminary information to guide a future definitive clinical trial, if indicated. Trial registration: STICK: ClinicalTrials.gov NCT02738736 (04/04/2016); COSIP: ClinicalTrials.gov NCT02458248 (15/05/2016)

Background and objectives Hyperphosphatemia is common among recipients of maintenance dialysis and is associated with a higher risk of mortality and cardiovascular events. A large randomized trial is needed to determine whether lowering phosphate concentrations with binders improves patient-important outcomes. To inform such an effort we conducted a pilot randomized controlled trial. Design, setting, participants, & measurements We conducted a randomized controlled trial of prevalent hemodialysis recipients already receiving calcium carbonate as a phosphate binder at five Canadian centers between March 31, 2014 and October 2, 2014. Participants were randomly allocated to 26 weeks of an intensive phosphate goal of 2.33–4.66 mg/dl (0.75–1.50 mmol/L) or a liberalized target of 6.20–7.75 mg/dl (2.00–2.50 mmol/L) by titrating calcium carbonate using a dosing nomogram. The primary outcome was the difference in the change in serum phosphate from randomization to 26 weeks. Results Fifty-three participants were randomized to the intensive group and 51 to the liberalized group. The median (interquartile range) daily dose of elemental calcium at 26 weeks was 1800 (1275–3000) mg in the intensive group, and 0 (0–500) mg in the liberalized group. The mean (SD) serum phosphate at 26 weeks was 4.53 (1.12) mg/dl (1.46 [0.36] mmol/L) in the intensive group and 6.05 (1.40) mg/dl (1.95 [0.45] mmol/L) in the liberalized group. Phosphate concentration in the intensive group declined by 1.24 (95% confidence interval, 0.75 to 1.74) mg/dl (0.40 [95% confidence interval, 0.24 to 0.56] mmol/L) compared with the liberalized group. There were no statistically significant differences between the two groups in the risk of hypercalcemia, hypocalcemia, parathyroidectomy, or major vascular events. Conclusions It is feasible to achieve and maintain a difference in serum phosphate concentrations in hemodialysis recipients by titrating calcium carbonate. A large trial is needed to determine if targeting a lower serum phosphate concentration improves patient-important outcomes.

Hamstring strain injuries (HSI) are among the most common injuries in field-based team sports with a high-speed running component. The implementation of the Nordic hamstring exercise (NHE) is a well-documented method of improving eccentric hamstring strength to mitigate the risk of HSI occurrence. Sprint training is specific to the injury mechanism and is thought to activate the hamstrings through maximal eccentric contractions. The purpose of this study was to compare the effects of sprint training and the NHE on eccentric hamstring strength and sprint performance.Twenty-eight participants (mean±SD age=16.21±1.34 years; height=1.75m±0.10m; body mass=68.5kg±12.1kg) completed an eccentric hamstring strength assessment and 40m sprint to assess acceleration and maximum speed. Participants were randomly allocated to either a NHE training or sprint training group. Two sessions per week for four-weeks of training was performed with baseline testing procedures repeated in the week following the intervention. Perceptions of soreness were recorded following the warm-up in each training session.Both the NHE (effect size=0.39, P0.05) and sprint training (effect size=0.29, P0.05) groups displayed significant gains in eccentric hamstring strength. The NHE group reported trivial improvements in sprint performance, whilst the sprint training group experienced a moderate improvement, specifically in maximum speed (ES=0.83 Moderate). Sprint training also produced greater perceptions of soreness than the NHE following a four-week training intervention, specifically before the start of the last session (P0.05).These findings indicate that sprint training had a beneficial effect for both eccentric hamstring strength and sprint performance, whilst also producing greater soreness than the NHE following the final training session. It was concluded that a four-week block of maximum speed training may have both an injury prevention and performance enhancement benefit.

Initiation of blockade of the renin-angiotensin system may cause an acute decrease in glomerular filtration rate (GFR): the prognostic significance of this is unknown. We did a post hoc analysis of patients with, or at risk for, vascular disease, in two randomized controlled trials: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND), whose median follow-up was 56 months. In 9340 patients new to renin-angiotensin system blockade, who were then randomized to renin-angiotensin system blockade, a fall in GFR of 15% or more at 2 weeks after starting renin-angiotensin system blockade was seen in 1480 participants (16%), with persistence at 8 weeks in 700 (7%). Both acute increases and decreases in GFR after initiation of renin-angiotensin system blockade were associated with tendencies, mostly not statistically significant, to increased risk of cardiovascular outcomes, which occurred in 1280 participants, and of microalbuminuria, which occurred in 864. Analyses of creatinine-based outcomes were suggestive of regression to the mean. In more than 3000 patients randomized in TRANSCEND to telmisartan or placebo, there was no interaction between acute change in GFR and renal or cardiovascular benefit from telmisartan. Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy.

Vitamin D plays an important role in calcium homeostasis and is essential for normal bone growth and remodeling. Previous studies of acutely ill and institutionalized older women in Galway revealed that vitamin D insufficiency is extremely common. We aimed to evaluate age and gender-related rates of vitamin D insufficiency and deficiency in adult patients attending their General Practitioners in the same region.A retrospective cohort study.General practices in Galway, a city located on the west coast of Ireland, latitude 53.17 North.A total of 15,708 consecutive blood samples from adults attending their General Practitioners between January 2013 and December 2014 were sent to the Clinical Biochemistry Laboratory in the University Hospital Galway for vitamin D level testing. 73% were from women.Data were collected and grouped according to age, sex and season. Vitamin D levels (25OHD) were categorised into deficiency (25nmol/L), insufficiency (25-50nmol/L) and sufficiency (50nmol/L).Median and interquartile range were reported as vitamin D levels were not normally distributed. Descriptive statistics were performed using STATA/MP 13.1 for Mac.While vitamin D levels were sufficient in 56.4% (n=8,496), they were insufficient in 32.4% (n=4,891) and deficient in 11.2% (n=1,691). Of the deficient group, 19%( 325) had levels15nmol/L consistent with profound deficiency. Men were more likely than women to be deficient (12% (n=489) vs. 10.9% (n=1,202)) and insufficient (38.0% (n=1,550) vs. 30.4% (n=3,341)) (p0.01). Highest rates of deficiency were seen in those 81-97 years (19.4% (n=136)) and 18-40 years (13.8% (n=543)), the former group showing less seasonal variation.Overall prevalence of insufficiency is similar to those in national and European studies published recently. However, there is a high possibility that those most vulnerable to vitamin D deficiency were underrepresented in this cohort, when results from previous studies in the same region are considered. Further prospective studies are needed to guide treatment with supplementation of vitamin D for appropriate subgroups.

Background Chronic kidney disease (CKD) is prevalent and associated with significant morbidity and mortality. Dietary modification may be an approach to reducing CKD. Design In this prospective cohort study, we evaluated the association between diet quality, sodium and potassium intakes, and major renal outcomes. A total of 544,635 community-dwelling adults, aged 51 to 70 years, living in 6 states and 2 urban areas in the United States, from the National Institutes of Health–American Association of Retired Persons Diet and Health Study. Using a food frequency questionnaire completed at baseline, we assessed diet quality using the Alternate Healthy Eating Index (AHEI), Healthy Eating Index (HEI), Mediterranean Diet Score (MDS), Recommended Food Score, and Dietary Approaches to Stop Hypertension (DASH) scores. This was also used to estimate daily sodium and potassium intakes. Main Outcome Measures Multivariable adjusted competing risks regression calculated sub-hazard ratios (sHRs) for a composite of death due to a renal cause and dialysis, with death due to a nonrenal cause as the competing event. Results During a mean of 14.3-year follow-up, a total of 4,848 participants died from a renal cause or initiated dialysis. Four diet quality scores (AHEI, HEI, MDS, and DASH) were significantly associated with the composite renal outcome; the Recommended Food Score was not. Compared to the lowest score quintile, the highest quintiles of AHEI (sHR 0.71; 95% confidence interval [CI] 0.65-0.79), HEI (sHR 0.82; 95% CI 0.74-0.91), MDS (sHR 0.84; 95% CI 0.74-0.95), and DASH (sHR 0.85; 95% CI 0.77-0.94) were associated with a reduced hazard of the composite. The highest sodium quintile (sHR 1.17; 95% CI 1.02-1.33 for sodium intake > 3.6 g/day) was associated with an increased hazard, whereas the highest potassium quintile (sHR 0.83 [0.73-0.95]) with a reduced hazard. Conclusions Our findings support an association between healthy dietary patterns and reduced risk of major renal outcomes and provide observational evidence to inform dietary guideline recommendations for CKD prevention.

Pre-gestational diabetes mellitus (PGDM) is associated with adverse outcomes. We aimed to examine pregnancies affected by PGDM; report on these pregnancy outcomes and compare outcomes for patients with type 1 versus type 2 diabetes mellitus; compare our findings to published Irish and United Kingdom (UK) data and identify potential areas for improvement.Between 2016 and 2018 information on 679 pregnancies from 415 women with type 1 Diabetes Mellitus and 244 women with type 2 diabetes was analysed. Data was collected on maternal characteristics; pregnancy preparation; glycaemic control; pregnancy related complications; foetal and maternal outcomes; unscheduled hospitalisations; congenital anomalies and perinatal deaths.Only 15.9% of women were adequately prepared for pregnancy. Significant deficits were identified in availability and attendance at pre-pregnancy clinic, use of folic acid, attaining appropriate glycaemic targets and appropriate retinal screening. The majority of pregnancies (n = 567, 83.5%) resulted in a live birth but the large number of infants born large for gestational age (LGA) (n = 280, 49.4%), born prematurely 37 weeks and requiring neonatal intensive care unit (NICU) admission continue to be significant issues.This retrospective cohort study identifies multiple targets for improvements in the provision of care to women with pre-gestational DM which are likely to translate into better pregnancy outcomes.

Background: A run-in period is often employed in randomised controlled trials to increase adherence to the intervention and reduce participant loss to follow-up in the trial population. However, it is uncertain whether use of a run-in period affects the magnitude of treatment effect. Methods: We will conduct a sensitive search for systematic reviews of cardiovascular preventative trials and a complete meta-analysis of treatment effects comparing cardiovascular prevention trials using a run-in period (“run-in trials”) with matched cardiovascular prevention trials that did not use a run-in period (“non-run-in trials”). We describe a comprehensive matching process which will match run-in trials with non-run-in trials by patient populations, interventions, and outcomes. For each pair of run-in trial and matched non-run-in trial(s), we will estimate the ratio of relative risks and 95% confidence interval. We will evaluate differences in treatment effect between run-in and non-run-in trials and our and our priamry outcome will be the ratio of relative risks for matched run-in and non-run-in trials for their reported cardiovascular composite outcome. Our secondary outcomes are comparisons of mortality, loss to follow up, frequency of adverse events and methodological quality of trials. Conclusions: This study will answer a key question about what influence a run-in period has on the magnitude of treatment effects in randomised controlled trials for cardiovascular prevention therapies.

ObjectiveTo evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (3.5 g potassium) in adults.DesignInternational prospective cohort study.Setting18 high, middle, and low income countries, sampled from urban and rural communities.Participants103 570 people who provided morning fasting urine samples.Main outcome measuresAssociation of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).ResultsMean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of 3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).ConclusionsThese findings suggest that the simultaneous target of low sodium intake (3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.

Background Urinary tract infections (UTIs) are the second most common infection presenting in the community. Clinical guidelines and decision aids assist health practitioners to treat a UTI; however, treatment practices vary due to patient needs and context of presentation. Numerous trials have evaluated the effectiveness of treatment interventions for UTI; however, it is difficult to compare the results between trials due to inconsistencies between reported outcomes. Poor choice of outcome measures can lead to impairment of evidence synthesis due to the inability to compare outcomes between trials with similar aims. Transparency in selecting and reporting outcomes can be mitigated through the development of an agreed minimum set of outcomes that should be reported in clinical trials, referred to as a core outcome set (COS). This paper presents the protocol for the development of a COS for interventions in the treatment of uncomplicated UTI in adults. Methods This COS development consists of three phases. Phase 1 is a systematic review, which aims to identify the core outcomes that have been reported in trials and systematic reviews of interventions treating uncomplicated UTI in adults. Phase 2 consists of a three-round online Delphi survey with stakeholders in the area of treatment interventions for UTI. The aim of this online Delphi survey is to achieve consensus on the importance of the outcomes emerging from Phase 1 of this research. Phase 3 is a consensus meeting to finalise the COS that should be reported in trials evaluating the effectiveness of interventions for the treatment of UTI. Discussion It is hoped that the development of a COS for interventions for the treatment of uncomplicated UTI in adults will be adopted as a minimum set of outcomes that should be reported and measured within this context. If the findings from clinical trials related to treatment interventions for UTI are to impact on policy and practice, it is important that the findings from different treatment interventions are comparable across trials. Electronic supplementary material The online version of this article (10.1186/s13063-019-3194-x) contains supplementary material, which is available to authorized users.

ObjectivesOlder patients with end-stage renal disease are willing participants in advance care planning but just over 10% are engaged in this process. Nephrologists fear such conversations may upset patients and so tend to avoid these discussions. This approach denies patients the opportunity to discuss their end-of-life care preferences. Many patients endure medically intensive end-of-life scenarios as a result. This study aims to explore the rationale underpinning nephrologists’ clinical decision-making in the management of older patients with end-stage renal disease and to make recommendations that inform policymakers and enhance advance care planning for this patient group.MethodsA qualitative interview study of 20 nephrologists was undertaken. Nephrologists were asked about their management of end-stage renal disease in older patients, conservative management, dialysis withdrawal and end-of-life care. Eligible participants were nephrologists working in Ireland. Five nephrologists participated in a recorded focus group and 15 nephrologists participated in individual digitally recorded telephone interviews. Semistructured interviews were conducted; thematic analysis was used to distil the results.ResultsThree key themes emerged: barriers to advance care planning; barriers to shared decision-making; and avoidance of end-of-life care discussion.ConclusionsAdvance care planning is not an integral part of the routine care of older patients with end-stage renal disease. Absence of formal training of nephrologists in how to communicate with patients contributes to poor advance care planning. Nephrologists lack clinical experience of conservatively managing end-stage renal disease and end-of-life care in older patients. Key policy recommendations include formal communication skills training for nephrologists and development of the conservative management service.

Background: Selecting outcome measures in cardiovascular prevention trials should be informed by their importance to selected populations. Major vascular event outcomes are usually prioritized in these trials with considerably less attention paid to cognitive and functional outcomes. Aim: To examine views on importance of outcome measures used in clinical trials. Design: Cross-sectional survey. Methods: Of 367 individuals approached, 280 (76%) participated: outpatients attending cardiovascular prevention clinics (n = 97), active retirement groups members (n = 75), medical students (n = 108). Participants were asked to rank, in order of importance, outcome measures, which may be included in cardiovascular prevention trials. Results were compared between two groups: = 65s (n = 104). Results: When asked what outcomes were most important to measure in cardiovascular prevention trials, respondents reported: death (31.6%) stroke (28.5%), dementia (26.9%), myocardial infarction (MI) (7.9%) and requiring nursing home (NH) care (5.1%). When asked the most relevant outcomes regarding successful ageing respondents reported; maintaining independence (32.4%), avoiding major illness (24.3%), good family life (23.6%), living as long as possible (15.8%), avoiding NH care (3.1%) and contributing to society (0.8%) as most important. When asked what outcome concerned them most about the future, respondents reported: dementia (32.6%), dependence (30.4%), death (12.8%), stroke (12.5%), cancer (6.2%) requiring NH care (4.8%) and MI (0.7%). Maintaining independence was considered most important in younger and older cohorts. Conclusion: Cognitive and functional outcomes are important patient-relevant outcomes, sometimes more important than major vascular events. Incorporating these outcomes into trials may encourage patient participation and adherence to preventative regimens.

Several glomerular diseases may occur in women of childbearing age. Pregnancy in such patients should be planned when the disease has been in remission for a minimum of 6 months to minimize maternal and fetal complications. Immunosuppressive agents should be optimized before conception to include those that are safe for pregnancy. The complexity of medical management when caring for these patients calls for a multidisciplinary team approach consisting of a nephrologist, rheumatologist, obstetrician, and pharmacist. This review will address the physiological changes of pregnancy that may affect glomerular disease presentation, activity, and diagnosis; specific glomerular diseases primary and secondary to systemic diseases in the context of pregnancy; fetal and maternal complications and long-term effects; diagnosis and differential diagnosis; and treatment strategies that are considered relatively safe with respect to fetal intrauterine exposure.

We thank Culic for his comments on our recent publication,1 but we wish to make 2 comments. First, we would like to clarify the assessment methods of physical exertion. Participants were asked about physical exertion in 2 ways: as a potential triggering event in the hour before acute myocardial infarction (AMI) and in the same hour on the previous day, and the usual level of physical activity. Therefore, we must clarify that we do not know whether mild to mderate physicial activity preceded AMI; instead we know that 24.6% of …

Preeclampsia, which affects approximately 5% of all pregnancies, is a pregnancy-specific disease characterized by hypertension (blood pressure ≥140/90 mmHg), as well as a systemic disease, which is commonly accompanied by proteinuria (≥300 mg/24-h urine collection) [1]. It occurs after 20 weeks of gestation, is a leading cause of fetal and maternal morbidity and mortality, and may be characterized by abnormal placental vessel formation [2] (placental preeclampsia), or by endothelial dysfunction that predates pregnancy in women with preexisting hypertension, diabetes, or obesity (maternal preeclampsia). [3] As a systemic disease, it is characterized by inflammation, oxidative stress, features of the metabolic syndrome, and a hypercoagulable state, as demonstrated by upregulation of multiple mediators of endothelial cell dysfunction [3]. Currently, there are no reliable early markers/predictors of preeclampsia. Its severe forms are characterized by renal insufficiency and pulmonary edema, and affected women are commonly treated by early termination of pregnancy, frequently leading to premature birth and high neonatal morbidity. Given its systemic character, renal, and cardiac involvement, we propose that preeclampsia is a cardiorenal syndrome (CRS) of pregnancy (Figure 1). Open image in new window Fig. 1 Preeclampsia as a cardiorenal syndrome in pregnancy. Cardiac and renal features and interactions that ultimately lead to cardiorenal pathophysiology in preeclampsia, with both immediate and long-term effects. AKI, acute kidney injury

Catheter-based renal sympathetic denervation (RSD) significantly reduces blood pressure in patients with resistant hypertension, who commonly have obstructive sleep apnoea (OSA). These patients are considered particularly responsive to the antihypertensive effects of RSD, but additional benefits of metabolic control on sleep apnoea severity have not been thoroughly investigated.The effect of RSD was evaluated prospectively in a cohort of patients with OSA (apnoea-hypopnea index (AHI) ≥15 events per hour and an Epworth Sleepiness Scale (ESS) score ≤9) and treatment resistant hypertension. Changes in blood pressure, polysomnographic parameters and metabolic indices were evaluated at baseline and six months post procedure.At baseline, mean office blood pressure was 166.3/92.8 (14.5/11.7) mmHg and mean ambulatory blood pressure was 154.0/87.3 (11.9/8.5) mmHg. At six months post RSD, mean office blood pressure reduced by 6.6/6.5 (1.9/2.0) mmHg (p 0.05) and mean ambulatory blood pressure reduced by 8.3/6.2 (2.3/2.0) (p 0.05). The mean AHI at baseline was 21.3 events/h and 20.5 events/h at six months post RSD, with a mean reduction of 0.9 events/h (95% CI -0.7-1.6, p = 0.39). Glucose at two hours/2 h following tolerance testing reduced by 1.14 mmol/L (95% CI 0.22-2.06, p = 0.03) but changes in other metabolic indices were not statistically significant.In patients with resistant hypertension and OSA, RSD resulted in modest improvements in blood pressure control, but no significant changes in sleep apnoea severity. Our study showed small increments in glucose tolerance but no significant changes in other markers of carbohydrate or lipid metabolism.

Background: Physical exertion, anger, and emotional upset are reported to trigger acute myocardial infarction (AMI). In the INTERHEART study, we explored the triggering association of acute physical activity and anger or emotional upset with AMI to quantify the importance of these potential triggers in a large, international population. Methods: INTERHEART was a case-control study of first AMI in 52 countries. In this analysis, we included only cases of AMI and used a case-crossover approach to estimate odds ratios for AMI occurring within 1 hour of triggers. Results: Of 12 461 cases of AMI 13.6% (n=1650) engaged in physical activity and 14.4% (n=1752) were angry or emotionally upset in the case period (1 hour before symptom onset). Physical activity in the case period was associated with increased odds of AMI (odds ratio, 2.31; 99% confidence interval [CI], 1.96–2.72) with a population-attributable risk of 7.7% (99% CI, 6.3–8.8). Anger or emotional upset in the case period was associated with an increased odds of AMI (odds ratio, 2.44; 99% CI, 2.06–2.89) with a population-attributable risk of 8.5% (99% CI, 7.0–9.6). There was no effect modification by geographical region, prior cardiovascular disease, cardiovascular risk factor burden, cardiovascular prevention medications, or time of day or day of onset of AMI. Both physical activity and anger or emotional upset in the case period were associated with a further increase in the odds of AMI (odds ratio, 3.05; 99% CI, 2.29–4.07; P for interaction Conclusions: Physical exertion and anger or emotional upset are triggers associated with first AMI in all regions of the world, in men and women, and in all age groups, with no significant effect modifiers.