The association of healthy lifestyle index score and the risk of renal cell cancer in the Netherlands cohort study.

BACKGROUND: Diet, alcohol, cigarette smoking, physical inactivity, and body mass index have been studied as risk factors for renal cell cancer (RCC). The joint effects of these lifestyle factors, captured as Healthy Lifestyle Index (HLI), were examined in one previous study. This study aims to investigate the association between HLI score and RCC risk in the prospective Netherlands Cohort Study (NLCS). METHODS: A case-cohort analysis (3,767 subcohort members, 485 cases) was conducted using NLCS data (n = 120,852). Data on aforementioned risk factors was used to calculate HLI score, ranging 0-20, with higher scores reflecting healthier lifestyles. RCC occurrence was obtained by record linkage to cancer registries. Multivariable-adjusted proportional hazard models were used to calculate Hazard Ratios (HR) and 95% Confidence Intervals (95%CI). RESULTS: Compared to participants in the unhealthiest HLI category, participants within the healthiest category had a lower RCC risk (HR = 0.79, 95%CI = 0.56-1.10, p for trend 0.045). A standard deviation (± 3-unit) increase in HLI score was not statistically significantly associated with a lower RCC risk (HR = 0.92, 95%CI = 0.83-1.01). This association was stronger after excluding diet or alcohol from the score, although confidence intervals overlap. CONCLUSIONS: Adherence to a healthy lifestyle was weakly, though not statistically significantly, associated with a lower RCC risk.

The prognostic value of quality of life in atrial fibrillation on patient value.

BACKGROUND: In this study, the prognostic value of AF-related quality of life (AFEQT) at baseline on Major Adverse Cardiovascular Events (MACE) and improvement of perceived symptoms (EHRA) was assessed. Furthermore, the relationship between QoL and AF-related hospitalizations was assessed. METHODS: A cohort of AF-patients diagnosed between November 2014 and October 2019 in four hospitals embedded within the Netherlands Heart Network were prospectively followed for 12 months. MACE was defined as stroke, myocardial infarction, heart failure and/or mortality. Subsequently, MACE, EHRA score improvement and AF-related hospitalizations between baseline and 12 months of follow-up were recorded. RESULTS: In total, 970 AF-patients were available for analysis. In analyses with patients with complete information on the confounder subset 36/687 (5.2%) AF-patients developed MACE, 190/432 (44.0%) improved in EHRA score and 189/510(37.1%) were hospitalized during 12 months of follow-up. Patients with a low AFEQT score at baseline more often developed MACE (OR(95%CI): 2.42(1.16-5.06)), more often improved in EHRA score (OR(95%CI): 4.55(2.45-8.44) and were more often hospitalized (OR(95%CI): 4.04(2.22-7.01)) during 12 months post diagnosis, compared to patients with a high AFEQT score at baseline. CONCLUSIONS: AF-patients with a lower quality of life at diagnosis more often develop MACE, more often improve on their symptoms and also were more often hospitalized, compared to AF-patients with a higher quality of life. This study highlights that the integration of patient-reported outcomes, such as quality of life, has the potential to be used as a prognostic indicator of the expected disease course for AF.

Etiologic heterogeneity of clear-cell and papillary renal cell carcinoma in the Netherlands Cohort Study.

At present, mostly case-control and retrospective studies have investigated the association between etiologic risk factors and the development of histologic subtypes of renal cell carcinoma (RCC). Therefore, we assessed the heterogeneity between body mass index (BMI), cigarette smoking, alcohol consumption and hypertension across clear-cell RCC (ccRCC) and papillary RCC (pRCC) risk in the prospective Netherlands Cohort Study on diet and cancer. In 1986, 120 852 participants aged 55 to 69 completed a self-administered questionnaire on diet and other risk factors for cancer. Participants were followed up for cancer through record linkage. Tumor histology was assessed through centralized revision by two experienced uropathologists. After 20.3 years of follow-up, 384 histologically verified RCC cases, including 315 ccRCC and 46 pRCC cases and 4144 subcohort members were eligible for case-cohort analysis. Hazard ratios and 95% confidence intervals were estimated by multivariable-adjusted proportional hazards models. Overall, BMI was associated positively with ccRCC risk, but inversely with pRCC risk. Cigarette smoking was associated with an increased ccRCC, but a decreased pRCC risk. Alcohol consumption was inversely associated with both ccRCC and pRCC risk. Hypertension was associated with an increased risk of both ccRCC and pRCC. Statistically significant etiologic heterogeneity was observed for BMI, BMI change since age 20, and smoking duration in current smokers across ccRCC and pRCC risk. In conclusion, we observed potential heterogeneity for BMI, BMI change and smoking duration across ccRCC and pRCC risk.

Cost-utility and cost-effectiveness analysis of a clinical medication review focused on personal goals in older persons with polypharmacy compared to usual care: Economic evaluation of the DREAMeR study.

AIMS: The ageing society may lead to increasing healthcare expenditure. A clinical medication review (CMR) could potentially reduce costs. The aim of this study is to perform a cost-utility and cost-effectiveness analysis from a societal perspective of a patient-centred CMR. METHODS: A trial-based cost-utility and cost-effectiveness analysis was performed as part of the DREAMeR study, a pragmatic controlled trial that randomised patients aged ≥70 years using at least seven drugs to either CMR or usual care. Over six months, healthcare consumption and drug use were collected to estimate costs, and effects were collected in terms of quality-adjusted life years (QALYs) measured with EQ-5D-5 L and EQ-VAS and as reduced health-related complaints with impact on patients' daily lives. RESULTS: The total mean costs per patient (n = 588) over six months were €4,189 ± 6,596 for the control group (n = 294) and €4,008 ± 6,678 for the intervention group (n = 294), including estimated intervention costs of €199 ± 67, which resulted in a mean incremental total cost savings of €181 for the intervention group compared to the control group. Compared to the control group, for the intervention group, the mean incremental QALYs over six months were: -0.00217 measured with EQ-5D and 0.003 measured with EQ-VAS. The incremental effect of reduced health-related complaints with impact was -0.34. There was a likelihood of >90% that the intervention was cost-saving. CONCLUSIONS: The benefits of a patient-centred CMR were inconsistent with no benefits on HR-QoL measured with EQ-5D-5 L and small benefits on HR-QoL measured with EQ-VAS and health-related complaints with impact on patients' daily lives. Additionally, a CMR could potentially be cost saving from a societal perspective.

Kidney stones and the risk of renal cell carcinoma and upper tract urothelial carcinoma: the Netherlands Cohort Study.

BACKGROUND: We examined the association between kidney stones and renal cell carcinoma (RCC) and upper tract urothelial carcinoma (UTUC) risk in the Netherlands Cohort Study on diet and cancer. METHODS: In total, 120,852 participants aged 55-69 completed a self-administered questionnaire on diet, medical conditions and other risk factors for cancer at baseline (1986). After 20.3 years of cancer follow-up 4352 subcohort members, 544 RCC cases and 140 UTUC cases were eligible for case-cohort analysis. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by multivariable-adjusted proportional hazards models. RESULTS: Kidney stones were associated with an increased RCC risk (HR: 1.39, 95% CI 1.05-1.84), vs. no kidney stones. Kidney stones were associated with an increased risk of papillary RCC (HR: 3.08, 95% CI 1.55-6.11), but not clear-cell RCC (HR: 1.14, 95% CI 0.79-1.65). UTUC risk was increased for participants with kidney stones (HR: 1.66, 95% CI 1.03-2.68). No heterogeneity of associations was found for UTUC in the ureter and renal pelvis. An early kidney stone diagnosis (≤40 years) was associated with an increased RCC and UTUC risk, compared to later diagnosis. CONCLUSION: Kidney stones were associated with increased papillary RCC risk, but not clear-cell RCC risk. No heterogeneity was found for UTUC subtypes.

Histologic re­evaluation of a population­based series of renal cell carcinomas from The Netherlands Cohort Study according to the 2022 ISUP/WHO classification.

The aim of the present study was to re-evaluate 457 renal cell carcinoma (RCC) cases from the Netherlands Cohort Study on Diet and Cancer (NLCS), a large population-based cohort, according to the new 2022 ISUP, Genitourinary Pathology Society and World Health Organisation (WHO) classifications to assess whether newly recognized subtypes of RCC could be found among these cases. These cases were initially evaluated according to the 2004 WHO classification, the Fuhrman grading system and the 3rd version of the Tumor-Node-Metastasis (TNM). Data on tumor size, laterality and date of diagnosis, among other clinicopathological characteristics, were obtained through record linkage with the Netherlands Cancer Registry and the Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief. Digital slides from the NLCS were reviewed by two urogenital pathologists according to the new ISUP grading and the 2022 WHO classification (5th edition). Immunohistochemistry staining for carbonic anhydrase IX was performed on cases with ambiguous morphology. A total of 373 cases of clear cell RCC (ccRCC), 61 cases of papillary RCC (pRCC), 13 cases of chromophobe RCC, 3 cases of collecting duct carcinoma and 4 cases of oncocytoma were identified. The subtyping showed no discrepancy with the previous diagnoses. A comparison of the WHO/ISUP grading to the original Fuhrman grading showed a similar grading in 245 (56.5%) cases of the total ccRCC and pRCC cases. The staging according to the novel TNM classification 8th edition showed a restaging in 286 cases (65.5%). Lymphovascular (microvascular) invasion (LVI) and tumor necrosis (TN) were present in 14.4% and 33.5% of the total number of cases, respectively. Furthermore, the presence of sarcomatoid differentiation in 5.1% and rhabdoid differentiation in 4.2% of the cases was observed. In conclusion, none of the newly accepted and emerging/provisional RCC entities were identified in the NLCS cases, which could be attributed to the high mean age (71.4 years) at diagnosis of the patients included in the present study. A restaging of the NLCS cases using the TNM 8th edition and regrading using ISUP grading was performed, which showed that it is possible to report on newer features, such as sarcomatoid differentiation and LVI, even in an old sample collection.

Reproductive and external hormonal factors and the risk of renal cell cancer in the Netherlands Cohort Study.

BACKGROUND: Several reproductive and hormonal factors, like age at menarche, parity, age at menopause, use of oral contraceptives and postmenopausal treatment, have been associated with the risk of renal cell cancer (RCC) in women, but results have not always been consistent. We therefore investigated the association between these factors and the risk of RCC in postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer. METHODS: Information on reproductive history, exogenous hormone use and gynecological surgery was obtained through a self-administered questionnaire at baseline in 1986. After 20.3 years of follow-up, 204 cases and 2280 subcohort members were available for case-cohort analysis. Multivariable hazard ratios (HR) were calculated using Cox Proportional Hazard analysis. RESULTS: Women who reported a hysterectomy had an increased RCC risk compared to women who did not (HR, 1.42, 95%CI, 1.01-2.00). Women with a natural age at menopause between 45 and 49 years compared to 50-54 years had an increased RCC risk (HR, 1.61; 95%CI, 1.10-2.35). RCC risk was slightly and not statistically significant increased among parous women with three or more children and age at first birth before 25 years compared to nulliparous women (HR, 1.36; 95% confidence interval (CI), 0.84-2.20). No associations were observed with RCC risk for age at menarche, use of oral contraceptives and use of hormonal replacement therapy. CONCLUSION: Hysterectomy and age at natural menopause were associated with an increased RCC risk. Other hormonal and reproductive factors and RCC risk were not increased. Further studies are required to establish the mechanism(s) that explain the observed association.

Evaluation of a seven gene mutational profile as a prognostic factor in a population-based study of clear cell renal cell carcinoma.

In this study, we investigate the influence of the seven genes (VHL, PBRM1, SETD2, BAP1, KDM5C, MTOR and TP53) most frequently mutated in clear cell renal cell cancer (ccRCC) on cancer-specific survival (CSS) in the prospective Netherlands Cohort Study on diet and cancer. DNA isolated from routinely archived formalin-fixed paraffin-embedded tumour blocks from 252 incident ccRCC cases was available for targeted next generation sequencing. Based on the sequencing quality and the completeness of information on clinical characteristics and follow-up, we could use 110 cases for survival analysis. The association with CSS for each mutated gene in these cases was tested using multivariable Cox proportional hazards models to estimate hazards ratios (HR) and confidence intervals (CIs), and we observed mutations in one or more of the seven genes in 64 out of 110 cases (58%). In the multivariable-adjusted analyses, mutations in VHL and PBRM1 were associated with better CSS (HRs (95% CI) 0.34 (0.13‒0.89) and 0.17 (0.04-0.66), respectively), although these results were not statistically significant after multiple testing correction. No association was observed for the other five genes, which may be attributable to limited power.

Age-dependency of EHRA improvement based on quality of life at diagnosis of atrial fibrillation.

BACKGROUND: In this study, the relationship between AF-related quality of life (AFEQT) at baseline in AF-patients and the improvement on perceived symptoms and general state of health (EHRA, European Heart Rhythm Association score) at 12 months was assessed across predefined age categories. METHODS: Between November 2014 and October 2019 patients diagnosed with AF de novo in four hospitals embedded within the Netherlands Heart Network were prospectively followed for 12 months. These AF-patients were categorized into quartiles based on their AFEQT score at diagnosis and EHRA score was measured at diagnosis and 12 months of follow-up. Stratified analyses were performed using age categories (<65 vs. ≥65 years; <75 vs. ≥75 years). RESULTS: In total, 203/483 (42.0%) AF-patients improved in EHRA score after 12 months of follow-up. AF-patients in the lowest AFEQT quartile were more likely to improve, compared to patients in the highest AFEQT quartile (OR [95%CI]:4.73 [2.63-8.50]). Furthermore, patients ≥65 years and patients <75 years at diagnosis with lower AFEQT scores at baseline were most likely to improve in EHRA score after 12 months, compared to similarly aged patients with higher AFEQT scores at baseline. CONCLUSION: The present study indicates that AF-patients with a lower quality of life at diagnosis were most likely to improve their EHRA score after 12 months. This effect was most prominent in patients ≥65 years of age and patients <75 years of age, compared to patients >65 and ≥75 years, respectively. Future research should focus on further defining characteristics of these age groups to enable the implementation of age-tailored treatment.

Regional implementation of atrial fibrillation screening: benefits and pitfalls.

Aims: Despite general awareness that screening for atrial fibrillation (AF) could reduce health hazards, large-scale implementation is lagging behind technological developments. As the successful implementation of a screening programme remains challenging, this study aims to identify facilitating and inhibiting factors from healthcare providers' perspectives. Methods and results: A mixed-methods approach was used to gather data among practice nurses in primary care in the southern region of the Netherlands to evaluate the implementation of an ongoing single-lead electrocardiogram (ECG)-based AF screening programme. Potential facilitating and inhibiting factors were evaluated using online questionnaires (N = 74/75%) and 14 (of 24) semi-structured in-depth interviews (58.3%). All analyses were performed using SPSS 26.0. In total, 16 682 screenings were performed on an eligible population of 64 000, and 100 new AF cases were detected. Facilitating factors included 'receiving clear instructions' (mean ± SD; 4.12 ± 1.05), 'easy use of the ECG-based device' (4.58 ± 0.68), and 'patient satisfaction' (4.22 ± 0.65). Inhibiting factors were 'time availability' (3.20 ± 1.10), 'insufficient feedback to the practice nurse' (2.15 ± 0.89), 'absence of coordination' (54%), and the 'lack of fitting policy' (32%). Conclusion: Large-scale regional implementation of an AF screening programme in primary care resulted in a low participation of all eligible patients. Based on the perceived barriers by healthcare providers, future AF screening programmes should create preconditions to fit the intervention into daily routines, appointing an overall project lead and a General Practitioner (GP) as a coordinator within every GP practice.

Preferences of patients regarding community pharmacy services: A discrete choice experiment.

BACKGROUND: The community pharmacy profession is in transition, with emphasis on the provision of cognitive pharmaceutical services (CPS). In contrast, previous research showed that the general public prefers more convenience related services. However, this was based on currently available services and not on innovative services. OBJECTIVE: To identify patients' preferences regarding innovative pharmacy services and whether they tend towards convenience related or CPS. DESIGN: Online survey using a discrete choice experiment (DCE). PARTICIPANTS: Participants were from the AMP pharmacy patient panel. MAIN OUTCOME MEASURES: Preferences (utility scores) and the identification of specific classes (latent class analysis). RESULTS: In total 2462 panel members (27.3%) filled out the completed the online DCE questionnaire. The majority of participants were male (54.1%) with an average age of 65.3 years and used on average 4.6 medicines. Four patient classes were distinguished based on preferences for services. Highly preferred were an online mediation record, prescription drugs for minor ailments without a doctors' prescription and clinical testing with diagnosis by the pharmacist. DISCUSSION AND CONCLUSION: The majority of participants tend towards a more CPS focused approach by the community pharmacist. Patients visiting community pharmacies can have a diverging set of preferences regarding services being provided. In daily practice, community pharmacists should provide both convenience and CPS related services to address this diverse set of preferences.

How does the general public balance convenience and cognitive pharmaceutical services in community pharmacy practice.

BACKGROUND: Community pharmacy is shifting its focus from traditional, product-focused roles to the provision of cognitive pharmaceutical services (CPS). Previous research has indicated that community pharmacists predominantly want to devote their capacity to CPS. Ideally, services provided also address users' needs. The general public's preferences regarding the services provided by community pharmacists are currently less understood. AIM: This study investigates the general public's preferences and perceived importance of CPS versus convenience in community pharmacy practice. METHOD: An online survey of 1.500 members of the Dutch Health Care Consumer Panel containing questions regarding preferences for CPS and convenience was distributed. Descriptive statistics and linear regression analysis were performed to investigate the relationship between preferences and participant characteristics. RESULTS: 516 panel members completed all questions regarding preferences and importance of the availability of services. The majority preferred convenience (68.2%) and a smaller proportion preferred CPS (27.7%). However, participants considered it important from a societal viewpoint that CPS is provided (45.0%). Participants who preferred CPS over convenience were generally older (p < 0.001) and used more medicines (p < 0.001). CONCLUSION: Convenience of community pharmacy services is most preferred by the general public. However, CPS is perceived as important, especially for elderly who use more medicines. Elderly patients who use more medicines more often rate CPS as more important than convenience. These findings suggest that community pharmacists should ensure that pharmacy logistics are organized efficiently before focusing on the provision of CPS.

Germline polymorphisms in the Von Hippel-Lindau and Hypoxia-inducible factor 1-alpha genes, gene-environment and gene-gene interactions and renal cell cancer.

We investigated the relationship between germline single nucleotide polymorphisms (SNPs) in Von Hippel-Lindau (VHL) and Hypoxia-inducible factor 1-alpha (HIF1A), and their gene-environment and gene-gene interactions, and clear-cell RCC (ccRCC) risk. Furthermore, we assessed the relationship between VHL SNPs and VHL promoter methylation. Three VHL polymorphisms and one HIF1A polymorphism were genotyped in the Netherlands Cohort Study. In 1986, 120,852 participants aged 55-69 completed a self-administered questionnaire on diet and lifestyle and toenail clippings were collected. Toenail DNA was genotyped using the Sequenom MassARRAY platform. After 20.3 years, 3004 subcohort members and 406 RCC cases, of which 263 ccRCC cases, were eligible for multivariate case-cohort analyses. VHL_rs779805 was associated with RCC (Hazard Ratio (HR) 1.53; 95% Confidence Interval (CI) 1.07-2.17) and ccRCC risk (HR 1.88; 95% CI 1.25-2.81). No associations were found for other SNPs. Potential gene-environment interactions were found between alcohol consumption and selected SNPs. However, none remained statistically significant after multiple comparison correction. No gene-gene interactions were observed between VHL and HIF1A. VHL promoter methylation was not associated with VHL SNPs. VHL SNPs may increase (cc)RCC susceptibility. No associations were found between gene-environment and gene-gene interactions and (cc)RCC risk and between VHL promoter methylation and VHL SNPs.

Balancing traditional activities and cognitive pharmaceutical services by community pharmacists: a work sampling study.

Background Community pharmacy is undergoing a transition, shifting focus from traditional roles to the provision of cognitive pharmaceutical services. However, traditional activities performed by community pharmacists reduce the amount of available time for implementing and providing such services. Therefore, hampering the community pharmacist in the transition. Objective The aim of this study was to identify characteristics of community pharmacists that spend a higher proportion of their time on cognitive pharmacy services and to identify activities that compete with time spent on such activities by community pharmacists. Setting Daily community pharmacy practice. Method Self-reporting work sampling using smartphone technology was used to register the activities of community pharmacists. Participating pharmacists recorded their current activity five times per working day for 6 weeks and also completed an online survey about baseline characteristics. Main outcome measure Time utilization. Results Ninety-one Dutch community pharmacists provided work-sampling data. The results showed that Dutch community pharmacists are predominantly spending less time on managerial activities when spending more time on cognitive services (from 25.7% to 14.5%, p = 0.016). Pharmacists who are spending more time on such services, want to spend even more time on direct patient contact compared to pharmacists who spend less time on it (p = 0.030). Conclusion This study shows that community pharmacists that spend more time on cognitive pharmacy services are devoting less time on managerial activities, logistics and other activities. Pharmacists spending more time on cognitive pharmaceutical services are mostly locum pharmacists or work at a pharmacy located in a residential area with largely older inhabitants.

How community pharmacists prioritize cognitive pharmaceutical services.

INTRODUCTION: There is broad consensus that community pharmacists should focus on the provision of pharmaceutical care. Studies, however, have shown that community pharmacists still spend a considerable amount of time on traditional activities such as dispensing instead of cognitive pharmaceutical services (CPS). It is not clear whether community pharmacists prefer their current time-utilization or if they are willing to spend more time on CPS. AIM: The aim of this study was to identify how community pharmacists ideally would prioritize CPS compared to other daily activities. METHODS: A cross-sectional study design with Q-methodology was used to identify different viewpoints regarding task prioritization. Community pharmacists were asked to rank a total of 48 daily activities. Data was collected online using FlashQ©. Q-sorts were analyzed by principal component factor analysis and varimax rotation using PQmethod 2.35. RESULTS: In total, 166 community pharmacists participated in this study. Three distinguishing groups were found based on task prioritization explaining 59% of the total variance among respondents. All groups ranked the provision of CPS as important, in differing degrees. Group 1 ranked CPS as most important and was also the group that contained most participants. Group 2 and 3 ranked quality assurance as most important with CPS as second. Logistics and pharmacy management were ranked low by all groups. DISCUSSION AND CONCLUSION: Community pharmacists rank the provision of CPS as important. So factors, probably other than task prioritization, are keeping the pharmacist from focusing on CPS in daily practice. In other studies, time constraints are mostly mentioned as major barrier. Activities such as logistics and pharmacy management are given less priority and should be delegated to supporting staff members as much as possible, to enable pharmacists to focus their available time on activities they deem important.

Pharmacy in transition: A work sampling study of community pharmacists using smartphone technology.

INTRODUCTION: The nature of community pharmacy is changing, shifting from the preparation and distribution of medicines to the provision of cognitive pharmaceutical services (CPS); however, often the provision of traditional services leaves little time for innovative services. This study investigated the time community pharmacists spend on the tasks and activities of daily practice and to what extent they are able to implement CPS-related services in daily practice. METHODS: Self-reporting work sampling was used to register the activities of community pharmacists. A smartphone application, designed specifically for this purpose, alerted participants to register their current activity five times per working day for 6 weeks. Participants also completed an online survey about baseline characteristics. RESULTS: Ninety-one Dutch community pharmacists provided work-sampling data (7848 registered activities). Overall, 51.5% of their time was spent on professional activities, 35.4% on semi-professional activities, and 13.1% on non-professional activities. The proportion of time devoted to CPS decreased during the workweek, whereas the time spent on traditional task increased. DISCUSSION AND CONCLUSION: This study shows it is feasible to collect work-sampling data using smartphone technology. Community pharmacists spent almost half of their time on semi-professional and non-professional activities, activities that could be delegated to other staff members. In practice, the transition to CPS is hampered by competing traditional tasks, which prevents community pharmacists from profiling themselves as pharmaceutical experts in daily practice.

Gut Colonization by Methanogenic Archaea Is Associated with Organic Dairy Consumption in Children.

The gut microbiota represents a complex and diverse ecosystem with a profound impact on human health, promoting immune maturation, and host metabolism as well as colonization resistance. Important members that have often been disregarded are the methanogenic archaea. Methanogenic archaea reduce hydrogen levels via the production of methane, thereby stimulating food fermentation by saccharolytic bacteria. On the other hand, colonization by archaea has been suggested to promote a number of gastrointestinal and metabolic diseases such as colorectal cancer, inflammatory bowel disease, and obesity. Archaea have been shown to be absent during infancy while omnipresent in school-aged children, suggesting that colonization may result from environmental exposure during childhood. The factors that determine the acquisition of methanogenic archaea, however, have remained undefined. Therefore, we aimed to explore determinants associated with the acquisition of the two main gastrointestinal archaeal species, Methanobrevibacter smithii and Methanosphaera stadtmanae, in children. Within the context of the KOALA Birth Cohort Study, fecal samples from 472 children aged 6-10 years were analyzed for the abundance of M. smithii and M. stadtmanae using qPCR. Environmental factors such as diet, lifestyle, hygiene, child rearing, and medication were recorded by repeated questionnaires. The relationship between these determinants and the presence and abundance of archaea was analyzed by logistic and linear regression respectively. Three hundred and sixty-nine out of the 472 children (78.2%) were colonized by M. smithii, and 39 out of the 472 children (8.3%) by M. stadtmanae. The consumption of organic yogurt (odds ratio: 4.25, CI95: 1.51; 11.95) and the consumption of organic milk (odds ratio: 5.58, CI95: 1.83; 17.01) were positively associated with the presence of M. smithii. We subsequently screened raw milk, processed milk, and yogurt samples for methanogens. We identified milk products as possible source for M. smithii, but not M. stadtmanae. In conclusion, M. smithii seems present in milk products and their consumption may determine archaeal gut colonization in children. For the first time, a large variety of determinants have been explored in association with gut colonization by methanogenic archaea. Although more information is needed to confirm and unravel the mechanisms in detail, it provides new insights on microbial colonization processes in early life.