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Recent research has focused on local context as crucial for inclusion. This paper focuses on schools’ prerequisites for inclusion and how such prerequisites can be theorised. We explore theoretical...

BACKGROUND AND AIMS Preliminary analyses suggest that absolute haemoglobin (Hb) values and rapid Hb changes may be associated with adverse outcomes in patients with anaemia of chronic kidney disease (CKD) treated with erythropoiesis-stimulating agents (ESAs) [1–3]. In this exploratory post-hoc analysis of the ASCEND-D trial, we investigated the association between absolute Hb values or Hb changes over 4-week periods and the occurrence of the first adjudicated major adverse cardiovascular event (MACE) in patients with CKD on dialysis who were treated with either daprodustat or ESAs. METHOD ASCEND-D was an event-driven cardiovascular outcomes trial conducted in over 30 countries that randomized 2964 CKD patients undergoing dialysis with a baseline Hb of 8.0–11.5 g/dL to receive oral, once-daily daprodustat (1487 patients), or a conventional ESA (epoetin alfa or darbepoetin; 1477 patients). Available doses were daprodustat 1–24 mg once-daily, epoetin alfa 1500–60 000 U total weekly dose, and darbepoetin 20–400 µg total 4-weekly dose. The co-primary endpoints of non-inferiority for first occurrence of adjudicated MACE and mean Hb change from baseline to weeks 28 through 52 were met and have been reported recently [4]. MACE was a composite of death from any cause, non-fatal myocardial infarction or non-fatal stroke. An independent clinical events committee, blind to treatment assignment, adjudicated the events. To examine the association of post-randomization absolute Hb values and Hb changes with first adjudicated MACE, we divided each patient's time in the study before a first MACE or end of follow-up into distinct 4-week intervals. We then calculated a post-randomization mean Hb value and Hb rate of increase or decrease at each 4-week interval. Separately for each treatment arm, we grouped these 4-week periods into quintiles of mean Hb values and Hb rates of increase or decrease (see Table 1), and calculated MACE rates for each quintile. This analysis did not include MACE that occurred before Week 4, as this was the time for the first scheduled post-randomization Hb collection. We used the average of Hb values imputed by the multiple imputation method to impute missing Hb values. RESULTS This analysis included 361 and 389 first MACE in the daprodustat and ESA treatment groups, respectively. When evaluating rates of the first occurrence of adjudicated MACE by absolute Hb value quintiles and irrespective of Hb change (‘All’ column in Figure 1), the MACE rate was higher in the low Hb quintile than in the high Hb quintile across both treatment groups. In the evaluation of rates of the first MACE by Hb change quintile and irrespective of absolute Hb value (‘All’ row in Figure 1), rates of MACE were comparable across Hb change quintiles within each treatment group. When MACE risk was evaluated by both absolute Hb value and Hb change quintiles, the highest MACE rate was observed in the lowest Hb quintile (Q1 row) with the largest positive change (Q5 increase column), and this was more pronounced in the ESA group. CONCLUSION This exploratory analysis suggests a possible association between Hb quintile and MACE outcome for both absolute and fluxes in Hb values. However, this analysis has several limitations including a small number of events in each quintile, possible confounding by severity of disease and the choice of assessment window. Further studies are needed to confirm these findings.

BACKGROUND AND AIMS Rapid changes in haemoglobin (Hb) following treatment with erythropoiesis-stimulating agents (ESAs) in patients with anaemia of chronic kidney disease (CKD) have been suggested to be associated with adverse outcomes [1–3]. This exploratory post-hoc analysis was performed to investigate the association between absolute Hb values or Hb changes over a 4-week period and the occurrence of first adjudicated major adverse cardiovascular event (MACE) in CKD patients not on dialysis who were treated with either daprodustat or darbepoetin. METHOD ASCEND-ND was an event driven, cardiovascular outcomes trial conducted in over 30 countries that randomized 3872 CKD patients not on dialysis with baseline Hb of 8–10 g/dL if not on a prior ESA, or 8–11 g/dL if receiving an ESA, to receive either oral, once-daily daprodustat (1937 patients) or subcutaneous darbepoetin (1935 patients). Available doses were daprodustat 1–24 mg once-daily and darbepoetin 20–400 µg total 4-weekly dose. The study was recently reported to have met the co-primary endpoints of non-inferiority for first occurrence of adjudicated MACE and mean Hb change from baseline to weeks 28 through 52 [4]. MACE was a composite of death from any cause, non-fatal myocardial infarction or non-fatal stroke, and events were adjudicated by an independent clinical events committee blinded to treatment assignment. In this exploratory post-hoc analysis, we examined the associations of post-randomization absolute Hb values and Hb changes categorized into quintiles (see Table 1) with first adjudicated MACE. Each patient's time in the study, prior to a first MACE or end of follow-up, was divided into distinct 4-week intervals, with each interval associated with a particular post-randomization Hb value and rate of change. Separately for each treatment group, these 4-week periods were grouped according to quintiles of Hb values, and MACE rates were calculated for each quintile. This analysis was repeated using quintiles derived from Hb rate of decrease and increase. MACEs that occurred prior to Week 4, the first scheduled post-randomization Hb collection, were not included in the analysis. RESULTS This analysis included 371 and 361 first occurrences of adjudicated MACE (‘first MACE’) in the daprodustat and darbepoetin treatment groups, respectively. When evaluating the rate of first MACE by absolute Hb value quintiles and irrespective of Hb change (‘All’ column in Figure 1), the MACE rate was higher in the low Hb quintile than in the high Hb quintile for both treatment groups (Figure 1). Evaluating the rate of first MACE by Hb change quintile and irrespective of absolute Hb value (‘All’ row in Figure 1), the rates of MACE were comparable across Hb change quintiles within each treatment group. When MACE risk was evaluated by both absolute Hb value and Hb change quintiles, the highest MACE rate was observed in the lowest Hb quintile (Q1 row) with the largest positive change (Q5 increase column), and this was more pronounced in the darbepoetin group. CONCLUSION This exploratory analysis suggests a possible association between Hb quintile and MACE outcome for both absolute and fluxes in Hb values. However, this analysis has several limitations including a small number of events in each quintile, possible confounding by severity of disease, and the choice of assessment window. Further studies will be needed to confirm these findings.

Rationale & Objective Persons with chronic kidney disease (CKD) are often unaware of their disease status. Efforts to improve CKD awareness may be most effective if focused on persons at highest risk for progression to kidney failure. Study Design Serial cross-sectional surveys. Setting & Participants Nonpregnant adults (aged ≥20 years) with CKD glomerular filtration rate categories 3-4 (G3-G4) who participated in the National Health and Nutrition Examination Survey from 1999 to 2016 (n = 3,713). Predictor 5-year kidney failure risk, estimated using the Kidney Failure Risk Equation. Predicted risk was categorized as minimal ( Outcome CKD awareness, defined by answering “yes” to the question “Have you ever been told by a doctor or other health professional that you had weak or failing kidneys?” Analytical Approach Prevalence of CKD awareness was estimated within each risk group using complex sample survey methods. Associations between Kidney Failure Risk Equation risk and CKD awareness were assessed using multivariable logistic regression. CKD awareness was compared with awareness of hypertension and diabetes during the same period. Results In 2011 to 2016, unadjusted CKD awareness was 9.6%, 22.6%, 44.7%, and 49.0% in the minimal-, low-, intermediate-, and high-risk groups, respectively. In adjusted analyses, these proportions did not change over time. Awareness of CKD, including among the highest risk group, remains consistently below that of hypertension and diabetes and awareness of these conditions increased over time. Limitations Imperfect sensitivity of the “weak or failing kidneys” question for ascertaining CKD awareness. Conclusions Among adults with CKD G3-G4 who have 5-year estimated risks for kidney failure of 5%

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International audience; Fatigue is one of the most highly prioritized outcomes for patients and clinicians, but remains infrequently and inconsistently reported across trials in hemodialysis. We convened an international Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) consensus workshop with stakeholders to discuss the development and implementation of a core outcome measure for fatigue. 15 patients/caregivers and 42 health professionals (clinicians, researchers, policy makers, and industry representatives) from 9 countries participated in breakout discussions. Transcripts were analyzed thematically. 4 themes for a core outcome measure emerged. Drawing attention to a distinct and all-encompassing symptom was explicitly recognizing fatigue as a multifaceted symptom unique to hemodialysis. Emphasizing the pervasive impact of fatigue on life participation justified the focus on how fatigue severely impaired the patient's ability to do usual activities. Ensuring relevance and accuracy in measuring fatigue would facilitate shared decision making about treatment. Minimizing burden of administration meant avoiding the cognitive burden, additional time, and resources required to use the measure. A core outcome measure that is simple, is short, and includes a focus on the severity of the impact of fatigue on life participation may facilitate consistent and meaningful measurement of fatigue in all trials to inform decision making and care of patients receiving hemodialysis.

Patients with end-stage renal disease (ESRD) requiring renal replacement have impaired health-related quality of life (HRQoL), and there is general consensus that HRQoL improves with successful transplant and evidence of improvement with frequent hemodialysis. This study reports changes in HRQoL associated with changes in treatment modality to daily hemodialysis (DHD) and transplant among patients requiring renal replacement. This cohort study had assessments at baseline and 6-month following modality change. Subjects were nondiabetic individuals receiving conventional hemodialysis who (a) remained on conventional hemodialysis (n = 13), (b) changed to daily hemodialysis (DHD) (n = 10), or (c) received a living donor transplant (n = 20). Thirty-four healthy controls were assessed once for comparison. HRQoL was measured using the Kidney Disease Quality of Life Instrument. The Physical Functioning and Physical Composite Scale scores were primary outcomes. Transplantation resulted in significant improvements in six of eight generic scales and the physical composite scale (PCS). Those changing to DHD had significant improvements in Physical Function and PCS scales. Those remaining on dialysis remained lower than controls on all scales except for Vitality; the transplant group remained lower than controls only on the Vitality and General Health scales. Transplant resulted in significant improvements in four of the seven disease-specific scales (symptoms, effects, and burden of kidney disease, work). DHD resulted in improvements in the effects of kidney disease. Modality change to transplant results in significant improvement in HRQoL, achieving levels similar to controls. Change to daily hemodialysis improves only select HRQoL domains and remains low in disease-specific domains.

Background Little is known about disability in early-stage chronic kidney disease (CKD). Study Design Cross-sectional national survey (National Health and Nutrition Examination Survey 1999-2006). Setting & Participants Community-based survey of 16,011 noninstitutionalized US civilian adults (aged ≥20 years). Predictor CKD, categorized as no CKD, stages 1 and 2 (albuminuria and estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m 2 ), and stages 3 and 4 (eGFR, 15-59 mL/min/1.73 m 2 ). Outcome Self-reported disability, defined by limitations in working, walking, and cognition and difficulties in activities of daily living (ADL), instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity. Measurements Albuminuria and eGFR assessed from urine and blood samples; disability, demographics, access to care, and comorbid conditions assessed using a standardized questionnaire. Results Age-adjusted prevalence of reported limitations generally was significantly greater with CKD: for example, difficulty with ADL was reported by 17.6%, 24.7%, and 23.9% of older (≥65 years) and 6.8%, 11.9%, and 11.0% of younger (20-64 years) adults with no CKD, stages 1 and 2, and stages 3 and 4, respectively. CKD also was associated with greater reported limitations and difficulty in other activities after age adjustment, including instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity. Other demographics, socioeconomic status, and access to care generally only slightly attenuated the observed associations, particularly in older individuals; adjustment for cardiovascular disease, arthritis, and cancer attenuated most associations such that statistical significance no longer was achieved. Limitations Inability to establish causality and possible unmeasured confounding. Conclusion CKD is associated with a higher prevalence of disability in the United States. Age and other comorbid conditions account for most, but not all, of this association.

The toxicity of tributyltin oxide (TBTO), a commonly used biocide in antifouling paints for ships, was studied in the copepod Acartia tonsa. The toxicity was assessed in short-term (120 h) experiments using egg production rate as test parameter. Impairment of egg production was observed at all the concentrations tested. After 120 h the egg production rate was reduced by 18,19 and 37% relative to control at the concentrations 0.01, 0.05 and 0.1 µg TBTO · 1-1, respectively. The concentrations of TBTO used in the test were lower than those that have been measured near Danish marinas. Thus, sublethal effects of organotin to pelagic copepods are likely to occur in these areas.