Socio-demographic and cultural factors related to non-participation in the Dutch colorectal cancer screening programme

BackgroundHigh participation rates are essential for a screening programme to be beneficial. To reach non-participants in a targeted manner, insight in characteristics of non-participants is needed. We investigated demographic differences between participants and non-participants in the Dutch faecal immunochemical test-based colorectal cancer (CRC) screening programme.MethodsIn this population-based cohort study, we included all invitees for CRC screening in 2018 and 2019. Participation status, birth year, and sex were extracted from the Dutch national screening information system and linked to demographic characteristics from Statistics Netherlands, including migration background, level of education, socioeconomic category, household composition, and household income. A multivariable logistic regression was used to assess the association between demographic factors and participation.ResultsA total of 4,383,861 individuals were invited for CRC screening in 2018 and 2019, of which 3,170,349 (72.3%) participated. Individuals were less likely to participate when they were single and/or living with others (single with other residents versus couple: odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.31–0.38), had a migration background (e.g. Moroccan migrant versus Dutch background: OR 0.43, 95% CI: 0.42–0.44), or had a low income (lowest versus highest quintile: OR 0.45, 95% CI: 0.44–0.45). Although to a lesser extent, non-participation was also significantly associated with being male, being younger, receiving social welfare benefits and having a low level of education.ConclusionWe found that individuals who were single and/or living with others, immigrants from Morocco or individuals with low income were the least likely to participate in the Dutch CRC screening programme. Targeted interventions are needed to minimise inequities in CRC screening.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Inflammation, sepsis severity and neurodevelopmental outcomes of late-onset sepsis in preterm neonates

Background: The aim of this study was to investigate the association between inflammatory biomarkers (C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6)) and sepsis severity (neonatal-Sequential-Organ-Failure-Assessment (nSOFA)) and neurodevelopmental outcomes at 2 years, among very preterm neonates. Methods: Data on preterm neonates (gestational age &lt;30 weeks) from 2016 until 2020 were reviewed. Outcomes of interest were NDI (no, mild, severe) and the motor and cognitive score on the Dutch-Bayley-Scales-of-Infant-and-Toddler-Development (Bayley-III-NL) assessed at the corrected age of 2 years. Logistic and linear regression analysis were used for categorical and continuous outcomes, respectively. All analyses were adjusted for gestational age, sex and birthweight-for-gestational-age SD-score. Results: In total 410 patients were eligible for analysis. Maximum CRP concentrations were associated with lower motor and cognitive scores (effect estimate −0.03 points,(95% CI −0.07; −0.00) and −0.03 points,(95% CI −0.06; −0.004), respectively) and increased risk of severe NDI (odds ratio (OR) 1.01, (95% CI 1.00; 1.01)). High nSOFA scores (≥4) during sepsis episodes were associated with an increased risk of mild NDI (OR 2.01, (95% CI 1.34; 3.03)). There were no consistent associations between IL-6, PCT and the outcomes of interest. Conclusion: High CRP concentrations and sepsis severity in preterm neonates seem to be associated with neurodevelopmental outcomes in survivors at the age of 2 years. Impact statement: The level of inflammation and sepsis severity are associated with neurodevelopmental outcome in preterm neonates at 2 years of corrected age.Sepsis is a major health issue in preterm neonates and can lead to brain damage and impaired neurodevelopment. Biomarkers can be determined to assess the level of inflammation. However, the relation of inflammatory biomarkers with neurodevelopmental outcome is not known.The level of inflammation and sepsis severity are related to neurodevelopmental outcome in preterm neonates. Maximum CRP concentration and high nSOFA scores are associated with an increased risk of neurodevelopmental impairment in survivors at the corrected age of 2 years.</p

“Macro transcobalamin causing raised vitamin B12: Case-based laboratory investigation"

Determination of plasma vitamin B12 (B12) is a frequently requested laboratory analysis, mainly employed to establish B12 deficiency. However, an increased level of B12 is a common unexpected finding that may be related to an increased concentration of one of the B12 binding proteins, haptocorrin or transcobalamin. This paper describes the extensive laboratory evaluation of a patient with an elevated level of plasma B12 with various well-established assays. Initial studies suggested the presence of a macromolecule consisting of haptocorrin bound B12. Specific determinations of the B12-binding proteins revealed normal amounts of haptocorrin but a markedly increase in both total and B12 saturated transcobalamin (holo-TC). The results are in accord with the presence of macro-transcobalamin. These experiments reveal that determination of the nature of the B12-macromolecules is troublesome due to differences in assays applied to measure these proteins. In addition, this publication creates awareness of macro-holo-TC as a cause of an unexplained increased B12 level

Effects of Short-Term Potassium Chloride Supplementation in Patients with Chronic Kidney Disease

Background : Observational studies suggest that adequate dietary potassium intake (90-120 mmol/day) may be renoprotective, but the effects of increasing dietary potassium and the risk of hyperkalemia are unknown. Methods : This is a pre-specified analysis of the run-in phase of a clinical trial in which 191 patients (age 68 +/- 11 years, 74% males, 86% European ancestry, eGFR 31 +/- 9 mL/min/1.73 m(2), 83% renin-angiotensin system inhibitors, 38% diabetes) were treated with 40 mmol KCl/day for two weeks. Results : KCl supplementation significantly increased urinary potassium excretion (72 +/- 24 to 107 +/- 29 mmol/day), plasma potassium (4.3 +/- 0.5 to 4.7 +/- 0.6 mmol/L), and plasma aldosterone (281 [198-431] to 351 [241-494] ng/L), but had no significant effect on urinary sodium excretion, plasma renin, blood pressure, eGFR, or albuminuria. Furthermore, KCl supplementation increased plasma chloride (104 +/- 3 to 105 +/- 4 mmol/L), reduced plasma bicarbonate (24.5 +/- 3.4 to 23.7 +/- 3.5 mmol/L) and urine pH (all P < 0.001), but did not change urinary ammonium excretion. Twenty-one participants (11%) developed hyperkalemia (plasma potassium 5.9 +/- 0.4 mmol/L). They were older and had higher baseline plasma potassium. Conclusions : In patients with CKD stage G3b-4, increasing dietary potassium intake to recommended levels with potassium chloride supplementation raises plasma potassium by 0.4 mmol/L. This may result in hyperkalemia in older patients or those with higher baseline plasma potassium. Longer-term studies should address whether cardiorenal protection outweighs the risk of hyperkalemia

Introducing heart rate variability monitoring combined with biomarker screening into a level IV NICU: a prospective implementation study

The aim of this study was to investigate the association between the implementation of a local heart rate variability (HRV) monitoring guideline combined with determination of inflammatory biomarkers and mortality, measures of sepsis severity, frequency of sepsis testing, and antibiotic usage, among very preterm neonates. In January 2018, a guideline was implemented for early detection of late-onset neonatal sepsis using HRV monitoring combined with determination of inflammatory biomarkers. Data on all patients admitted with a gestational age at birth of &lt; 32 weeks were reviewed in the period January 2016–June 2020 (n = 1,135; n = 515 pre-implementation, n = 620 post-implementation). Outcomes of interest were (sepsis-related) mortality, sepsis severity (neonatal sequential organ failure assessment (nSOFA)), sepsis testing, and antibiotic usage. Differences before and after implementation of the guideline were assessed using logistic and linear regression analysis for binary and continuous outcomes respectively. All analyses were adjusted for gestational age and sex. Mortality within 10 days of a sepsis episode occurred in 39 (10.3%) and 34 (7.6%) episodes in the pre- and post-implementation period respectively (P = 0.13). The nSOFA course during a sepsis episode was significantly lower in the post-implementation group (P = 0.01). We observed significantly more blood tests for determination of inflammatory biomarkers, but no statistically significant difference in number of blood cultures drawn and in antibiotic usage between the two periods.Conclusion: Implementing HRV monitoring with determination of inflammatory biomarkers might help identify patients with sepsis sooner, resulting in reduced sepsis severity, without an increased use of antibiotics or number of blood cultures.Medical Instruments & Bio-Inspired Technolog

Supplementary Material for: Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease

Background/Aims: Dietary potassium (K+) has beneficial effects on blood pressure and cardiovascular (CV) outcomes. Recently, several epidemiological studies have revealed an association between urinary K+ excretion (as proxy for dietary intake) and better renal outcomes in subjects with chronic kidney disease (CKD). To address causality, we designed the “K+ in CKD” study. Methods: The K+ in CKD study is a multicenter, randomized, double blind, placebo-controlled clinical trial aiming to include 399 patients with hypertension, CKD stage 3b or 4 (estimated glomerular filtration rate [eGFR] 15–44 mL/min/1.73 m2), and an average eGFR decline &gt; 2 mL/min/1.73 m2/year. As safety measure, all included subjects will start with a 2-week open-label phase of 40 mmol potassium chloride daily. Patients who do not subsequently develop hyperkalemia (defined as serum K+ &gt;5.5 mmol/L) will be randomized to receive potassium chloride, potassium citrate (both K+ 40 mmol/day), or placebo for 2 years. The primary end point is the difference in eGFR after 2 years of treatment. Secondary end points include other renal outcomes (&gt; 30% decrease in eGFR, doubling of serum creatinine, end-stage renal disease, albuminuria), ambulatory blood pressure, CV events, all-cause mortality, and incidence of hyperkalemia. Several measurements will be performed to analyze the effects of potassium supplementation, including body composition monitoring, pulse wave velocity, plasma renin and aldosterone concentrations, urinary ammonium, and intracellular K+ concentrations. Conclusion: The K+ in the CKD study will demonstrate if K+ supplementation has a renoprotective effect in progressive CKD, and whether alkali therapy has additional beneficial effects

Advanced-stage CRC incidence patterns following the phased implementation of the CRC screening programme in the Netherlands

Background and aims: From 2014, the Dutch colorectal cancer (CRC) faecal immunochemical testing-based screening programme was gradually rolled out by birth cohort. We evaluated changes in advanced-stage CRC incidence by timing of invitation to further strengthen the evidence for the effectiveness of CRC screening. Methods: Data on advanced-stage CRC incidence in the period 2010–2019 by invitation cohort were collected through the Netherlands Cancer Registry. Crude rates of advanced-stage CRC incidence and cumulative advanced-stage CRC incidence were calculated. Observed advanced-stage CRC incidence and cumulative advanced-stage CRC incidence were compared with expected advanced-stage CRC incidence and cumulative advanced-stage CRC incidence by invitation cohort using trend lines extrapolating data prior to the introduction of screening. Results: For the invitation cohort that was first invited for screening in 2014, advanced-stage CRC incidence increased before the introduction of screening from 94.1 to 124.7 per 100,000 individuals in the period 2010–2013. In 2014, the observed increase was higher than in preceding years, to 184.9 per 100,000 individuals. Hereafter, a decrease in incidence was observed to levels below expected incidence based on trends before the introduction of screening. A similar pattern was observed for invitation cohorts in subsequent years, coinciding with the first invitation to the screening programme. In 2019, the observed incidence for all invitation cohorts remained below expected incidence. The cumulative advanced-stage CRC incidence in the 2014–2016 invitation cohorts was significantly lower than the expected cumulative CRC incidence in the period 2010–2019. Conclusions: In the period 2014–2019, an increase in advanced-stage CRC incidence was observed for all invitation cohorts first invited for screening, followed by a decrease below expected incidence, following the pattern of the phased implementation. The cumulative advanced-stage CRC incidence in invitation cohorts invited for screening multiple times was lower than expected based on trends from the pre-screening era. These findings support a causal relationship between the introduction of the Dutch screening programme and a decrease in advanced-stage CRC incidence

Supplementary Material for: Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease

Background/Aims: Dietary potassium (K+) has beneficial effects on blood pressure and cardiovascular (CV) outcomes. Recently, several epidemiological studies have revealed an association between urinary K+ excretion (as proxy for dietary intake) and better renal outcomes in subjects with chronic kidney disease (CKD). To address causality, we designed the “K+ in CKD” study. Methods: The K+ in CKD study is a multicenter, randomized, double blind, placebo-controlled clinical trial aiming to include 399 patients with hypertension, CKD stage 3b or 4 (estimated glomerular filtration rate [eGFR] 15–44 mL/min/1.73 m2), and an average eGFR decline &gt; 2 mL/min/1.73 m2/year. As safety measure, all included subjects will start with a 2-week open-label phase of 40 mmol potassium chloride daily. Patients who do not subsequently develop hyperkalemia (defined as serum K+ &gt;5.5 mmol/L) will be randomized to receive potassium chloride, potassium citrate (both K+ 40 mmol/day), or placebo for 2 years. The primary end point is the difference in eGFR after 2 years of treatment. Secondary end points include other renal outcomes (&gt; 30% decrease in eGFR, doubling of serum creatinine, end-stage renal disease, albuminuria), ambulatory blood pressure, CV events, all-cause mortality, and incidence of hyperkalemia. Several measurements will be performed to analyze the effects of potassium supplementation, including body composition monitoring, pulse wave velocity, plasma renin and aldosterone concentrations, urinary ammonium, and intracellular K+ concentrations. Conclusion: The K+ in the CKD study will demonstrate if K+ supplementation has a renoprotective effect in progressive CKD, and whether alkali therapy has additional beneficial effects

Colorectal cancer incidence, mortality, tumour characteristics, and treatment before and after introduction of the faecal immunochemical testing-based screening programme in the Netherlands: a population-based study

Background: In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 μg haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before and after introduction of this screening programme. Methods: We did a retrospective, observational, population-based study in the Netherlands and gathered CRC incidence data from the Netherlands Cancer Registry from Jan 1, 2010, to Dec 31, 2019, in people aged 55 years or older. Patients with a CRC diagnosis between Jan 1, 2014, and Dec 31, 2018, in the Netherlands Cancer Registry were linked with the nationwide registry of histopathology and cytopathology (PALGA) to identify mode of detection (ie, screening-detected vs clinically detected). We calculated age-standardised CRC incidence rates and used data from Statistics Netherlands to calculate CRC-related mortality in 2010–19. We compared localisation, stage distribution, and treatment of screening-detected CRCs with clinically detected CRCs diagnosed in 2014–18 in patients aged 55–75 years. Findings: Between Jan 1, 2010, and Dec 31, 2019, 125 215 CRCs were diagnosed in individuals aged 55 years or older and were included in the analyses for CRC incidence. Before the introduction of the screening programme, the age-standardised CRC incidence rate was 214·3 per 100 000 population in 2013 in people aged 55 years or older. After the introduction of the screening programme, this rate initially increased to 259·2 per 100 000 population in 2015, and subsequently decreased to 181·5 per 100 000 population in 2019. Age-standardised incidence rates for advanced CRCs (stage III and IV) were 117·0 per 100 000 population in 2013 and increased to 122·8 per 100 000 population in 2015; this rate then decreased to 94·7 per 100 000 population in 2018. Age-standardised CRC mortality decreased from 87·5 deaths per 100 000 population in 2010 to 64·8 per 100 000 population in 2019. Compared with clinically detected CRCs, screening-detected CRCs were more likely to be located in the left side of the colon (48·6% vs 35·2%) and to be detected at an early stage (I or II; 66·7% vs 46·2%). Screening-detected CRCs were more likely to be treated by local excision compared with clinically detected CRCs, and this finding persisted when stage I CRCs were analysed separately. Interpretation: After introduction of this national screening programme, a decrease in overall and advanced-stage CRC incidence was observed. In view of this observation, together with the observed shift to detection at earlier stages and more screening-detected CRCs being treated by local excision, we might cautiously conclude that, in the long-term, faecal immunochemical testing-based screening could ultimately lead to a decrease in CRC-related morbidity and mortality. Funding: None