Less meat in the shopping basket. The effect on meat purchases of higher prices, an information nudge and the combination: a randomised controlled trial.

BACKGROUND: Reduced meat consumption benefits human and planetary health. Modelling studies have demonstrated the significant health and environmental gains that could be achieved through fiscal measures targeting meat. Adding other interventions may enhance the effect of a fiscal measure. The current study aimed to examine the effect of higher meat prices, an information nudge and a combination of both measures on meat purchases in a three-dimensional virtual supermarket. METHODS: A parallel designed randomised controlled trial with four conditions was performed. Participants (≥ 18 years) were randomly assigned to the control condition or one of the experimental conditions: a 30% price increase for meat ('Price condition'), an information nudge about the environmental impact of meat production and consumers' role in that regard ('Information nudge condition') or a combination of both ('Combination condition'). Participants were asked to shop for their household for one week. The primary outcome was the difference in the total amount of meat purchased in grams per household per week. RESULTS: Between 22 June 2020 and 28 August 2020, participants were recruited and randomly assigned to the control and experimental conditions. The final sample included 533 participants. In the 'Combination condition', - 386 g (95% CI: - 579, - 193) meat was purchased compared with the 'Control condition'. Compared to the 'Control condition' less meat was purchased in the 'Price condition' (- 144 g (95%CI: - 331, 43)), although not statistically significant, whereas a similar amount of meat was purchased in the 'Information nudge condition' (1 g (95%CI: - 188, 189)). CONCLUSION: Achieving the most pronounced effects on reduced meat purchases will require a policy mixture of pricing and informational nudging. Less meat is purchased in a virtual supermarket after raising the meat price by 30% combined with an information nudge. The results could be used to design evidence-based policy measures to reduce meat purchases. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register identifier NL8628 . Registered on 18/05/2020. ICTRP Search Portal (who.int) NTR (trialregister.nl).

The patient's view on rare disease trial design - a qualitative study.

BACKGROUND: Clinical trials in rare diseases are more challenging than trials in frequent diseases. Small numbers of eligible trial participants, often complicated by heterogeneity among rare disease patients, hamper the design and conduct of a 'classical' Randomized Controlled Trial. Therefore, novel designs are developed by statisticians. However, it is important to be aware of possible design aspects that may jeopardize the feasibility of trial conduct. If the burden of participation is considered out of proportion by patients or parents, recruitment may fail or participants may drop out before trial completion. In order to maximize the chance of success of trials in small populations, it is important to know which aspects of trial design are considered important by patients. RESULTS: We have interviewed all ten members of the Patient Think Tank (PTT) of the ASTERIX project, a European research consortium on methodology for clinical trials in small populations. The PTT members are rare disease patient representatives who have completed extensive training in clinical trial methodology. We have analyzed the interviews qualitatively according to Grounded Theory using a thematic analysis, and we structured the topics in four chronologically ordered themes: 1. Involvement in trial design; 2. Opinions on trial design; 3. Trial participation; 4. Phase after the trial. Our main findings are that the PTT-members recommend that patients are involved in trial design from an early stage on, and have influence on the outcomes and measurement instruments that are chosen in the trial, the length of the study, the choice of participants, and the information that is sent to potential participants. Also, according to the PTT-members, patient groups should consider setting up disease registries, placebo groups should be minimized, and more education on clinical trials is advised. CONCLUSIONS: Rare disease patient representatives who have been educated about clinical trial methodology think it is important to involve patient representatives in research at an early stage. They can be of advice in trial design in such a way that the ratio of potential benefit and burden of trial participation as well as the chosen outcome measures and in- and exclusion criteria are optimized.

Prospective associations of age at complementary feeding and exclusive breastfeeding duration with body mass index at 5-6 years within different risk groups.

BACKGROUND: Children with overweight or obesity are at risk for developing obesity in adulthood. Certain maternal characteristics, such as ethnicity, education, body mass index (BMI) or neighbourhood, are determinants for childhood overweight risk. There are large variations in how mothers differing in these characteristics feed their infants. Therefore, associations of age at complementary feeding, exclusive breast feeding duration with childhood overweight may differ in these groups. Understanding these associations would be essential to develop overweight prevention strategies. OBJECTIVES: The objective of this study is to study the associations of age at complementary feeding, exclusive breastfeeding duration with BMI-standard deviation score (SDS) at 5-6 years within risk groups. METHODS: Using data from the Amsterdam Born Children and their Development study, a population-based birth cohort (n = 4495), we formed groups of children at varying risk of overweight according to maternal characteristics of ethnicity, education, pre-pregnancy BMI and neighbourhood. Linear and logistic regression analyses were conducted. RESULTS: Complementary feeding after 5 months of age was associated with lower BMI-SDS in children of mothers of Dutch ethnicity (B: -0.12; 95% CI: -0.21, -0.04), medium-level education (-0.19; -0.30, -0.08), normal BMI (-0.08; -0.16, -0.01) and high-risk neighbourhood (-0.16; -0.29, -0.02). Compared with exclusive breastfeeding for <3 months, exclusive breastfeeding for ≥6 months was associated with lower BMI-SDS in groups of medium-level education (-0.28; 0.44, -0.11), normal BMI (-0.18; -0.29, -0.08) and medium-risk (-0.18; -0.33, -0.04) and high-risk (-0.22; -0.42, -0.02) neighbourhoods. CONCLUSIONS: Associations between infant feeding practices and childhood BMI may differ between risk groups, implying that overweight prevention strategies should be group-specific.

Actual and perceived nursing workload and the complexity of patients with total hip arthroplasty.

BACKGROUND: Little is known about the relation between patient complexity and nursing care of total hip arthroplasty (THA) patients. To improve patient care and hospital logistics, the aim of this study is to gain insight into the relation between patient complexity and the nursing staff's actual and perceived workload at an orthopedic ward during admission for a THA. DESIGN: Prospective cohort study of 45 THA patients in the year 2014. Duration and type of nursing care activities were recorded during the first postoperative morning. A questionnaire was used to analyze the perceived workload of the nursing staff. Both actual and perceived workload were analyzed for their relation with patient complexity, expressed in the American Society of Anesthesiologists (ASA) score, Charlson comorbidity index (CCI), Katz Activities of Daily Life score (Katz-ADL) and Body Mass Index (BMI). RESULTS: No relation was found between actual workload and measures for patient complexity. The perceived workload of the nursing staff was related to two complexity measures: ASA (r=0.71; p<0.001) and CCI (r=0.65; p=0.002). CONCLUSION: Patient comorbidity is related to the perceived workload of the nursing staff during admission for a THA. Patient complexity is not related to actual workload. This study gives a first insight into the relation between patient comorbidity and nursing staff workload, to try to improve staffing numbers at the ward as well as patient care in the process.

Heritability of tic disorders: a twin-family study.

BACKGROUND: Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. METHOD: In an extended twin-family design, we analysed lifetime tic data reported by adult mono- and dizygotic twins (n = 8323) and their family members (n = 7164; parents and siblings) from 7311 families in the Netherlands Twin Register. We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes. Heritability was estimated by genetic structural equation modeling for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. RESULTS: Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between 0.25 and 0.37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment or non-additive genetic effects. CONCLUSIONS: Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSM-IV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.

Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women.

OBJECTIVE: To investigate the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD). DESIGN: Prospective cohort study. SUBJECTS: A total of 16 165 women aged 49-70 years without prior CVD. SUBJECTS were breast cancer screening participants in the PROSPECT-EPIC cohort, which is 1 of the 2 Dutch contributions to the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Each participant completed a validated food frequency questionnaire. Folate intake was calculated with the Dutch National Food Database. Betaine and choline intakes were calculated with the USDA database containing choline and betaine contents of common US foods. Data on coronary heart disease (CHD) events and cerebrovascular accident (CVA) events morbidity data were obtained from the Dutch Centre for Health Care Information. RESULTS: During a median follow-up period of 97 months, 717 women were diagnosed with CVD. After adjustment, neither folate, nor betaine, nor choline intakes were associated with CVD (hazard ratios for highest versus lowest quartile were 1.23 (95% confidence interval 0.75; 2.01), 0.90 (0.69; 1.17), 1.04 (0.71; 1.53), respectively). In a subsample of the population, high folate and choline intakes were statistically significantly associated with lower homocysteine levels. High betaine intake was associated with slightly lower high-density lipoprotein (HDL)-cholesterol concentrations. CONCLUSION: Regular dietary intakes of folate, betaine and choline were not associated with CVD risk in post-menopausal Dutch women. However, the effect of doses of betaine and choline beyond regular dietary intake--for example, via supplementation or fortification--remains unknown.

Effects of betaine intake on plasma homocysteine concentrations and consequences for health.

High plasma concentrations of homocysteine may increase risk of cardiovascular disease. Folic acid lowers plasma homocysteine by 25% maximally, because 5-methyltetrahydrofolate is a methyl donor in the remethylation of homocysteine to methionine. Betaine (trimethylglycine) is also a methyl donor in homocysteine remethylation, but effects on homocysteine have been less thoroughly investigated. Betaine in high doses (6 g/d and higher) is used as homocysteine-lowering therapy for people with hyperhomocysteinemia due to inborn errors in the homocysteine metabolism. Betaine intake from foods is estimated at 0.5-2 g/d. Betaine can also be synthesized endogenously from its precursor choline. Studies in healthy volunteers with plasma homocysteine concentrations in the normal range show that betaine supplementation lowers plasma fasting homocysteine dose-dependently to up to 20% for a dose of 6 g/d of betaine. Moreover, betaine acutely reduces the increase in homocysteine after methionine loading by up to 50%, whereas folic acid has no effect. Betaine doses in the range of dietary intake also lower homocysteine. This implies that betaine can be an important food component that attenuates homocysteine rises after meals. If homocysteine plays a causal role in the development of cardiovascular disease, a diet rich in betaine or choline might benefit cardiovascular health through its homocysteine-lowering effects. However betaine and choline may adversely affect serum lipid concentrations, which can of course increase risk of cardiovascular disease. However, whether the potential beneficial health effects of betaine and choline outweigh the possible adverse effects on serum lipids is as yet unclear.

Effect of resistant starch on potential biomarkers for colonic cancer risk in patients with colonic adenomas: a controlled trial.

Resistant starch decreases the concentration of secondary bile acids in the feces and the proliferation rate of colonic mucosal cells in healthy volunteers. This may reduce the risk of colon cancer. We investigated 23 patients with recently removed colonic adenoma(s) in a controlled parallel trial. They consumed 45 g of maltodextrin per day as placebo for four weeks and were randomly assigned to either 45 g of native amylomaize starch, containing 28 g of resistant starch type II or 45 g of maltodextrin for another four weeks. No effect on colorectal cell proliferation, fecal wet and dry weights, pH, and short-chain fatty acid excretion was seen. The bile acid concentration in fecal water decreased by 15% (P = 0.048) and the percentage secondary bile acids decreased by 14% (P = 0.002) on resistant starch relative to placebo. Whether this has a substantial role in colon cancer prevention in these patients remains to be established.

Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans.

BACKGROUND: In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d. OBJECTIVE: We studied whether chlorogenic acid affects plasma total homocysteine concentrations in humans. For comparison we also studied the effects of black tea rich in polyphenols and of quercetin-3-rutinoside, a major flavonol in tea and apples. DESIGN: In this crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic acid, 4 g black tea solids containing approximately 4.3 mmol polyphenols and comparable to approximately 2 L strong black tea, 440 mg (0.7 mmol) quercetin-3-rutinoside, or a placebo daily. Each subject received each of the 4 treatments for 7 d, in random order. RESULTS: Total homocysteine in plasma collected 4-5 h after supplement intake was 12% (1.2 micromol/L; 95% CI: 0.6, 1.7) higher after chlorogenic acid and 11% (1.1 micromol/L; 95% CI: 0.6, 1.5) higher after black tea than after placebo. Total homocysteine in fasting plasma collected 20 h after supplement intake was 4% (0.4 micromol/L; 95% CI: 0.0, 0.8) higher after chlorogenic acid and 5% (0.5 micromol/L; 95% CI: 0.0, 0.9) higher after black tea than after placebo. Quercetin-3-rutinoside did not significantly affect homocysteine concentrations. CONCLUSIONS: Chlorogenic acid, a compound in coffee, and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid could be partly responsible for the higher homocysteine concentrations observed in coffee drinkers. Whether these effects on homocysteine influence cardiovascular disease risk remains to be established.

Red wine is a poor source of bioavailable flavonols in men.

Red wine is a source of polyphenolic antioxidants, of which flavonols such as quercetin are representatives. Red wine might therefore prevent LDL oxidation and atherosclerosis. However, data on the bioavailability of flavonols from wine are lacking. Therefore, we compared the bioavailability of flavonols, especially quercetin, from red wine with that from the major dietary sources, yellow onions and black tea. Twelve healthy men consumed 750 mL red wine, 50 g fried onions or 375 mL of black tea, each for 4 d in random order. These supplements provided similar amounts of quercetin (14-16 mg). There was a washout period of 3 d between each period of supplementation. The plasma quercetin concentration after the consumption of wine was lower than that after onions (P: < 0.05) and not different from that after tea. Urinary excretion of quercetin after wine did not differ from that after onions and was higher than that after tea (P: < 0.05). We conclude that flavonols from red wine are absorbed. However, because one glass of red wine provides fewer available flavonols than one portion of onions or one glass of tea, red wine appears to be a poorer source of flavonols than these other two sources.

Chlorogenic acid and caffeic acid are absorbed in humans.

Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the absorption of chlorogenic acid and caffeic acid in humans are lacking. We determined the absorption of chlorogenic acid and caffeic acid in a cross-over study with 4 female and 3 male healthy ileostomy subjects. In such subjects, degradation by the colonic microflora is minimal and absorption can be calculated as the amount ingested minus the amount excreted in ileostomy effluent. The ileostomy subjects ingested 2.8 mmol chlorogenic acid and 2.8 mmol caffeic acid on separate days in random order and subsequently collected ileostomy fluid and urine for 24 h. Absorption of chlorogenic acid was 33 +/- 17% (mean +/- SD) and of caffeic acid 95 +/- 4%. Traces of the ingested chlorogenic acid and 11% of the ingested caffeic acid were excreted in urine. Thus, one third of chlorogenic acid and almost all of the caffeic acid were absorbed in the small intestine of humans. This implies that part of chlorogenic acid from foods will enter into the blood circulation, but most will reach the colon.

Bioavailabilities of quercetin-3-glucoside and quercetin-4'-glucoside do not differ in humans.

The flavonoid quercetin is an antioxidant which occurs in foods mainly as glycosides. The sugar moiety in quercetin glycosides affects their bioavailability in humans. Quercetin-3-rutinoside is an important form of quercetin in foods, but its bioavailability in humans is only 20% of that of quercetin-4'-glucoside. Quercetin-3-rutinoside can be transformed into quercetin-3-glucoside by splitting off a rhamnose molecule. We studied whether this 3-glucoside has the same high bioavailability as the quercetin-4'-glucoside. To that end we fed five healthy men and four healthy women (19-57 y) a single dose of 325 micromol of pure quercetin-3-glucoside and a single dose of 331 micromol of pure quercetin-4'-glucoside and followed the plasma quercetin concentrations. The bioavailability was the same for both quercetin glucosides. The mean peak plasma concentration of quercetin was 5.0+/-1.0 micromol/L (+/-SE) after subjects had ingested quercetin-3-glucoside and 4.5+/-0.7 micromol/L after quercetin-4'-glucoside consumption. Peak concentration was reached 37 +/-12 min after ingestion of quercetin-3-glucoside and 27+/-5 min after quercetin-4'-glucoside. Half-life of elimination of quercetin from blood was 18.5+/-0.8 h after ingestion of quercetin-3-glucoside and 17.7+/-0.9 h after quercetin-4'-glucoside. We conclude that quercetin glucosides are rapidly absorbed in humans, irrespective of the position of the glucose moiety. Conversion of quercetin glycosides into glucosides is a promising strategy to enhance bioavailability of quercetin from foods.