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We test whether the length of an indefinite horizon, or that the horizon is indefinite as opposed to finite, affects cooperation in repeated 3x3 Red Queen Games. With our participant population, and our experimental program and procedures, the length of the indefinite horizon significantly affects cooperation in the Prisoner's Dilemma. However, it does not significantly affect cooperation in the Red Queen Game. Nor does the indefiniteness of the horizon significantly affect cooperation in this latter game. Our results highlight the importance of learning in indefinite games with even slightly larger strategy spaces than the Prisoner's Dilemma.

Background and ObjectivesThere is uncertainty about the association between alcohol consumption and stroke, particularly for low-moderate intake. We explored these associations in a large international study.MethodsINTERSTROKE, a case-control study, is the largest international study of risk factors for acute stroke. Alcohol consumption was self-reported and categorized by drinks/week as low (1–7), moderate (7–14 for females and 7–21 for males), or high (>14 for females and >21 for males). Heavy episodic drinking (HED) was defined as >5 drinks on ≥1 day per month. Multivariable conditional logistic regression was used to determine associations.ResultsWe included 12,913 cases and 12,935 controls; 25.0% (n = 6,449) were current drinkers, 16.7% (n = 4,318) former drinkers, and 58.3% (n = 15,076) never drinkers. Current drinkers were younger, male, smokers, active, and with higher-paid occupations. Current drinking was associated with all stroke (OR 1.14; 95% CI 1.04–1.26) and intracerebral hemorrhage (ICH) (OR 1.50, 95% CI 1.21–1.84) but not ischemic stroke (OR 1.06; 95% CI 0.95–1.19). HED pattern was associated with all stroke (OR 1.39; 95% CI 1.21–1.59), ischemic stroke (OR 1.29; 95% CI 1.10–1.51), and ICH (OR 1.76; 95% CI 1.31–2.36). High level of alcohol intake was consistently associated with all stroke, ischemic stroke, and ICH. Moderate intake was associated with all stroke and ICH but not ischemic stroke. Low alcohol intake was not associated with stroke overall, but there were regional differences; low intake was associated with reduced odds of stroke in Western Europe/North America (OR 0.66; 95% CI 0.45–0.96) and increased odds in India (OR 2.18; 95% CI 1.42–3.36) (p-interaction 0.037). Wine consumption was associated with reduced odds of all stroke and ischemic stroke but not ICH. The magnitudes of association were greatest in those without hypertension and current smokers.DiscussionHigh and moderate intake were associated with increased odds of stroke, whereas low intake was not associated with stroke. However, there were important regional variations, which may relate to differences in population characteristics of alcohol consumers, types or patterns of consumption.

Purpose Increasing potassium intake, especially in populations with low potassium intake and high sodium intake, has emerged as an important population-level intervention to reduce cardiovascular events. Current guideline recommendations, such as those made by the World Health Organisation, recommend a potassium intake of > 3.5 g/day. We sought to determine summary estimates for mean potassium intake and sodium/potassium (Na/K) ratio in different regions of the world. Methods We performed a systematic review and meta-analysis. We identified 104 studies, that included 98 nationally representative surveys and 6 multi-national studies. To account for missingness and incomparability of data, a Bayesian hierarchical imputation model was applied to estimating summary estimates of mean dietary potassium intake (primary outcome) and sodium/potassium ratio. Results Overall, 104 studies from 52 countries were included (n = 1,640,664). Mean global potassium intake was 2.25 g/day (57 mmol/day) (95% credible interval (CI) 2.05–2.44 g/day), with highest intakes in Eastern and Western Europe (mean intake 3.53g/day, 95% CI 3.05–4.01 g/day and 3.29 g/day, 95% CI 3.13–3.47 g/day, respectively) and lowest intakes in East Asia (mean intake 1.89 g/day; 95% CI 1.55–2.25 g/day). Approximately 31% (95% CI, 30–41%) of global population included have an estimated potassium intake > 2.5 g/day, with 14% (95% CI 11–17%) above 3.5 g/day. Conclusion Global mean potassium intake (2.25 g/day) falls below current guideline recommended intake level of > 3.5 g/day, with only 14% (95% CI 11–17%) of the global population achieving guideline-target mean intake. There was considerable regional variation, with lowest mean potassium intake reported in Asia, and highest intake in Eastern and Western Europe.

BACKGROUND: While low sodium intake (40 years with stable blood pressure (BP), without heart failure or postural hypotension were randomised to intensive dietary counselling (target sodium intake

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.

Rationale & Objective Adaptive design methods are intended to improve the efficiency of clinical trials and are relevant to evaluating interventions in dialysis populations. We sought to determine the use of adaptive designs in dialysis clinical trials and quantify trends in their use over time. Study Design We completed a novel full-text systematic review that used a machine learning classifier (RobotSearch) for filtering randomized controlled trials and adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Setting & Study Populations We searched MEDLINE (PubMed) and ClinicalTrials.gov using sensitive dialysis search terms. Selection Criteria for Studies: We included all randomized clinical trials with patients receiving dialysis or clinical trials with dialysis as a primary or secondary outcome. There was no restriction of disease type or intervention type. Data Extraction & Analytical Approach We performed a detailed data extraction of trial characteristics and a completed a narrative synthesis of the data. Results 57 studies, available as 68 articles and 7 ClinicalTrials.gov summaries, were included after full-text review (initial search, 209,033 PubMed abstracts and 6,002 ClinicalTrials.gov summaries). 31 studies were conducted in a dialysis population and 26 studies included dialysis as a primary or secondary outcome. Although 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 (6.12% in 2009 to 0.43% in 2019, with a mean of 1.82%). Group sequential designs were the most common type of adaptive design method used. Adaptive design methods affected the conduct of 50.9% of trials, most commonly resulting in stopping early for futility (41.2%) and early stopping for safety (23.5%). Acute kidney injury was studied in 32 trials (56.1%), kidney failure requiring dialysis was studied in 24 trials (42.1%), and chronic kidney disease was studied in 1 trial (1.75%). 27 studies (47.4%) were supported by public funding. 44 studies (77.2%) did not report their adaptive design method in the title or abstract and would not be detected by a standard systematic review. Limitations We limited our search to 2 databases (PubMed and ClinicalTrials.gov ) due to the scale of studies sourced (209,033 and 6,002 results, respectively). Conclusions Adaptive design methods are used in dialysis trials but there has been a decline in their relative use over time.

We experimentally explore indefinitely repeated contests. Theory predicts more cooperation, in the form of lower expenditures, in indefinitely repeated contests with a longer expected time horizon, and our data support this prediction, although this result attenuates with contest experience. Theory also predicts more cooperation in indefinitely repeated contests compared to finitely repeated contests of the same expected length, and we find empirical support for this. Finally, theory predicts no difference in cooperation across indefinitely repeated winner-take-all and proportional-prize contests, yet we find evidence of less cooperation in the latter, though only in longer treatments with more contests played. Our paper extends the experimental literature on indefinitely repeated games to contests and, more generally, contributes to an infant empirical literature on behavior in indefinitely repeated games with "large" strategy spaces.

Introduction: Measuring patient-reported information in stroke research is challenging. To overcome this, use of proxy respondents is often a necessary strategy. In this study, we report on use and effect of proxy respondents on patient case-mix in a large international epidemiologic stroke study (INTERSTROKE). Methods: This was a cross-sectional study of 13,458 cases of acute first stroke in 32 countries. A standardized study questionnaire recording behavioural cardiovascular risk factors was administered to the patient, and if unable to communicate adequately, a valid proxy, or both. We used logistic regression to evaluate the association of age, sex, education, occupation, stroke severity, and region with need for proxy respondent, and report odds ratio (OR) with 95% confidence interval (CI). Results: Among 13,458 participants with acute stroke, questionnaires were completed by patients alone in 41.4% (n = 5,573), combination of patient and proxy together in 21.7% (n = 2,918), and proxy alone in 36.9% (n = 4,967). Use of proxy alone was greater in participants with severe stroke (4.7% with modified-Rankin score of 0 vs. 80.5% in those with score 5; OR 187.13; 95% CI: 119.61–308.22), older persons (43.8% of those aged 80 years and over vs. 33.2% of those aged less than 40 years; age per decade OR 1.09; 95% CI: 1.06–1.12), women (40.7% vs. 34.3% of men; OR 1.32 95% CI: 1.22–1.43), and those less educated (58.9% of those never educated vs. 25.7% of those who attended third level education; OR 7.84; 95% CI: 6.78–9.08). Conclusion: Use of proxy respondents enhances the generalizability of international research studies of stroke, by increasing representation of women, patients with severe stroke, older age, and lower education.

We report laboratory experiments investigating the cyclicality of profit‐enhancing investment in a competitive environment. In our setting, optimal investment is counter‐cyclical when investment costs fall following market downturns. However, we do not observe counter‐cyclical investment. Instead, we see much less strategic behavior than our rational investment model anticipates. Our participants exhibit what Porter (1980) terms a competitive blind spot, and heuristic investment models where individuals invest a fixed percentage of their liquidity, or a fixed percentage of anticipated market demand, better fit our data than does optimal investment. We also report a control treatment without cost changes and a treatment with asymmetric investment liquidity. Both of these extensions support our main result.

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 Uncomplicated urinary tract infections (UTIs) are amongst the most frequent infections presenting in the outpatient setting. A growing number of clinical trials are assessing the most effective treatment interventions for uncomplicated UTI. Due to the heterogeneity of the outcomes reported in these trials, however, comparing these outcomes is challenging. Objectives Identify the core outcomes that have been reported in trials and systematic reviews of interventions treating uncomplicated UTI in adults. Methods We conducted a systematic search for core outcomes used to evaluate treatments of UTIs. We searched the Cochrane Database of Systematic Reviews, PubMed and Embase. One researcher independently screened each article for inclusion, and the Core Outcome Set for treatment of Urinary Tract Infections (COSUTI) team acted as second reviewers. All included articles were screened by two reviewers. All outcomes were extracted verbatim, and similar outcomes were grouped into domains and subdomains. Results In total, 334 outcomes were reported across 41 papers, the average number of outcomes reported being 8. Outcomes were categorized across 18 domains, the majority of which were related to clinical cure outcomes. Many outcomes varied in the timepoints within which the outcome was measured and reported. Conclusions Comparing the outcomes of trials investigating uncomplicated UTI treatment remains challenging due to the difference in outcomes currently reported. Consistency of reporting of outcomes would be improved by developing a minimum number of consistent outcomes that should be reported in all trials.

ObjectivesLow health literacy among older adults is associated with limited engagement in end-of-life care plans, more hospitalisations and excess mortality. Frequently, older patients derive no survival benefit from dialysis and quality of life often deteriorates with dialysis. Older dialysis patients’ values and wishes are often unknown during key healthcare decision-making and many endure medically intensive end-of-life interventions . The objectives of this study were to examine older dialysis patients’ understanding of haemodialysis, their engagement in end-of-life care planning and their satisfaction with life on haemodialysis.Methods15 older dialysis patients participated in qualitative semi-structured interviews in two haemodialysis units . Thematic saturation was reached. Thematic analysis, applied inductively, distilled the data.ResultsThemes identified included disempowerment which reflected limited health literacy, poor advance care planning compromised well-being and haemodialysis compromised their core values.ConclusionHealth literacy among older dialysis patients appeared poor, patient empowerment was limited and participation in shared decision-making and advance care planning suboptimal. Consequently, complex healthcare decision-making, including haemodialysis may jeopardise patients’ core values. These findings have significant implications for the validity of the informed consent process prior to dialysis initiation. Improved health literacy through enhanced patient education and better communication skills for clinicians are necessary to promote patient participation in shared decision-making. Clinician training to facilitate discussion of patients’ values and wishes will help guide clinicians and patients towards healthcare decisions most concordant with individual core values. This will optimise patient-centred care.

Although most current guidelines recommend a daily sodium intake of less than 2.3 g/day, most people do not have a reliable estimate of their usual sodium intake. In this review, we describe the different methods used to estimate sodium intake and discuss each method in the context of specific clinical or research questions. We suggest the following classification for sodium measurement methods: preingestion measurement (controlled intake), peri-ingestion measurement (concurrent), and postingestion measurement. On the basis of the characteristics of the available tools, we suggest that: validated 24-h recall methods are a reasonable approach to estimate sodium intake in large epidemiologic studies and individual clinical counselling sessions, methods (such as single 24-h urine collection, single-time urine collection, or 24-h recall methods), are of value in population-level estimation of mean sodium intake, but are less suited for individual level estimation and a feeding-trial design using a controlled diet is the most valid and reliable method for establishing the effect of reducing sodium to a specific intake target in early phase clinical trials. By considering the various approaches to sodium measurement, investigators and public health practitioners may be better informed in assessing the health implications of sodium consumption at the individual and population level.

Patients with end-stage renal disease (ESRD) requiring hemodialysis (HD) have an increased risk of thrombotic events and bleeding. Antisense reduction of factor XI (FXI) with IONIS-FXIThis multicenter study enrolled 49 patients receiving HD in 2 parts. First, 6 participants (pharmacokinetics [PK] cohort) received 1 open-label 300 mg dose of IONIS-FXIThe PK of IONIS-FXIIONIS-FXI

We explore the intersection of growth theory and the theory of the firm with an experiment. Economic growth is possible in our experiment when agents specialize to exploit increasing returns. We find that low opportunity costs are sufficient for Marshallian internal economies, but that Marshallian external economies are slow to emerge in four probing treatment conditions. Transaction costs do not hamper external economies as we anticipated prior to collecting data. When external economies falter, it is because new ideas of more extensive specialization fail to emerge. Ideas make further divisions of the division of labour—and thus economic growth—possible. Conversely, a lack of ideas make further divisions of labour and economic growth impossible. Our data reveal how the likelihood of new ideas is inseparably tied to the existing extent of specialization.

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).

This paper examines the relationship between product innovation and the success of price collusion using novel laboratory experiments. Average market prices in low innovation experiments are significantly higher than those in high innovation, but otherwise identical experiments. This price difference is attributed to low innovation experimental subjects' greater common market experience. The data illustrate how collusion can be perceived as the "only way to make it" in low innovation markets where product innovation is not a viable strategy for increasing profits. They suggest that product homogeneity can be a proximate cause, and product innovation an ultimate cause, of collusion.

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 and Aims Adaptive design methods are intended to improve efficiency of clinical trials, and relevant to evaluating interventions in dialysis populations. We sought to quantify the use of adaptive design clinical trials in dialysis. Method We completed a full text systematic review and adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Our review utilised included a novel machine learning classifier and full text systematic review. We searched MEDLINE (Pubmed) and performed a detailed data extraction of trial characteristics and a narrative synthesis of the data. Results 50 studies, available as 66 articles, were included after full text review. 31 studies were conducted in a dialysis population and 23 studies had renal replacement therapy as a primary or secondary outcome. Group sequential designs were the most common type of adaptive design method used in dialysis randomized clinical trials and in general adaptive designs usage is increasing over time. Acute Kidney Injury (AKI) was studied in 27 (54%) of trials, End Stage Kidney Disease (ESKD) was studied in 22 (44%) of trials and Chronic Kidney Disease (CKD) was studied in one trial (2%). The most common country of lead author was the United States of America in n=20 (40%) of studies. 26 (52%) studies 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 review involving title and abstract searches. Conclusion Adaptive design methods are infrequently used in dialysis randomized control trials.

Jumps occur frequently in basketball and can be executed from a single-leg take-off following a run-up or bilaterally from a standing start. Understanding the type of jumps performed in competition and how different muscular qualities influence their performance, informs training prescription. Firstly, to quantify the occurrence of different jump types performed in competition an analysis of 15 semi-professional basketball games was undertaken. Secondly, to understand the influence of muscular qualities on performance of different jump types, Semi-professional male basketball players (N=17) performed jump tests; standing vertical jump, running vertical jumps with a double leg take-off (RVJ2) and a single leg take-off (RVJ1) and tests of lower-body speed-strength; reactive strength index (RSI) from a drop jump, counter movement jump (CMJ) and squat jump. A stationary approach was employed for 69%, a running approach for 26% and a one-step approach for 5%. RVJ1 displayed non-significant (P=0.07) moderate correlation with jump height attained from the CMJ (r=0.439) and a very large (r =.806) significant (P

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

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)

Solvent alleged that chlorinated benzene contamination detected in Solvent's offsite groundwater recovery wells was 98% due to releases from the neighboring Olin chlorobenzene production facility and only 2% due to Solvent's nearby chlorinated benzene production facility. However, Solvent's position was complicated by the fact that it had acknowledged that its operations had impacted site contamination levels. Solvent's position was that the onsite contamination was partially due to Olin, but it faced an uphill struggle because the New York State Department of Environmental Conservation (NYSDEC) had assigned Solvent responsibility for the Hot Spot cleanup at the Olin site. However, Solvent was able to recover virtually the entire amount of its Hot Spot costs attributable to chlorinated benzenes from Olin, as well as the full percentage of allocation they requested from Olin for the Solvent site through the useof chemical tracers such as benzene hexachloride (BHC).