| 1. |
- Abel, Marianne Hope, et al.
(författare)
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Insufficient maternal iodine intake is associated with subfecundity, reduced foetal growth, and adverse pregnancy outcomes in the Norwegian Mother, Father and Child Cohort Study.
- 2020
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Ingår i: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Severe iodine deficiency impacts fertility and reproductive outcomes. The potential effects of mild-to-moderate iodine deficiency are not well known. The aim of this study was to examine whether iodine intake was associated with subfecundity (i.e. > 12 months trying to get pregnant), foetal growth, and adverse pregnancy outcomes in a mild-to-moderately iodine-deficient population.We used the Norwegian Mother, Father and Child Cohort Study (MoBa) and included 78,318 pregnancies with data on iodine intake and pregnancy outcomes. Iodine intake was calculated using an extensive food frequency questionnaire in mid-pregnancy. In addition, urinary iodine concentration was available in a subsample of 2795 pregnancies. Associations were modelled continuously by multivariable regression controlling for a range of confounding factors.The median iodine intake from food was 121 μg/day and the median urinary iodine was 69 μg/L, confirming mild-to-moderate iodine deficiency. In non-users of iodine supplements (n = 49,187), low iodine intake (< 100-150 μg/day) was associated with increased risk of preeclampsia (aOR = 1.14 (95% CI 1.08, 1.22) at 75 vs. 100 μg/day, p overall < 0.001), preterm delivery before gestational week 37 (aOR = 1.10 (1.04, 1.16) at 75 vs. 100 μg/day, p overall = 0.003), and reduced foetal growth (- 0.08 SD (- 0.10, - 0.06) difference in birth weight z-score at 75 vs. 150 μg/day, p overall < 0.001), but not with early preterm delivery or intrauterine death. In planned pregnancies (n = 56,416), having an iodine intake lower than ~ 100 μg/day was associated with increased prevalence of subfecundity (aOR = 1.05 (1.01, 1.09) at 75 μg/day vs. 100 μg/day, p overall = 0.005). Long-term iodine supplement use (initiated before pregnancy) was associated with increased foetal growth (+ 0.05 SD (0.03, 0.07) on birth weight z-score, p < 0.001) and reduced risk of preeclampsia (aOR 0.85 (0.74, 0.98), p = 0.022), but not with the other adverse pregnancy outcomes. Urinary iodine concentration was not associated with any of the dichotomous outcomes, but positively associated with foetal growth (n = 2795, p overall = 0.017).This study shows that a low iodine intake was associated with restricted foetal growth and a higher prevalence of preeclampsia in these mild-to-moderately iodine-deficient women. Results also indicated increased risk of subfecundity and preterm delivery. Initiating iodine supplement use in pregnancy may be too late.
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| 2. |
- Alehagen, Urban, et al.
(författare)
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Supplementation with selenium and coenzyme Q10 in an elderly Swedish population low in selenium - positive effects on thyroid hormones, cardiovascular mortality, and quality of life
- 2024
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL).METHODS: Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses.RESULTS: In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group.CONCLUSIONS: Supplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency.TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.
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| 3. |
- Aleksandrova, Krasimira, et al.
(författare)
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Development and validation of a lifestyle-based model for colorectal cancer risk prediction : the LiFeCRC score
- 2021
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.
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| 4. |
- Bae, J. B., et al.
(författare)
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Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study
- 2020
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Ingår i: Bmc Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. Conclusion Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.
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| 5. |
- Bai, Ge, et al.
(författare)
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Frailty and the risk of dementia : is the association explained by shared environmental and genetic factors?
- 2021
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association. Methods The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41-97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment. Results A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE e4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age. Conclusions A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.
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| 6. |
- Bell, Max, et al.
(författare)
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Individual and neighborhood risk factors of hospital admission and death during the COVID-19 pandemic : a population-based cohort study
- 2023
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The coronavirus disease 2019 (COVID-19) disproportionately affects minority populations in the USA. Sweden — like other Nordic countries — have less income and wealth inequality but lacks data on the socioeconomic impact on the risk of adverse outcomes due to COVID-19.Methods: This population-wide study from March 2020 to March 2022 included all adults in Stockholm, except those in nursing homes or receiving in-home care. Data sources include hospitals, primary care (individual diagnoses), the Swedish National Tax Agency (death dates), the Total Population Register “RTB” (sex, age, birth country), the Household Register (size of household), the Integrated Database For Labor Market Research “LISA” (educational level, income, and occupation), and SmiNet (COVID data). Individual exposures include education, income, type of work and ability to work from home, living area and living conditions as well as the individual country of origin and co-morbidities. Additionally, we have data on the risks associated with living areas. We used a Cox proportional hazards model and logistic regression to estimate associations. Area-level covariates were used in a principal component analysis to generate a measurement of neighborhood deprivation. As outcomes, we used hospitalization and death due to COVID-19.Results: Among the 1,782,125 persons, male sex, comorbidities, higher age, and not being born in Sweden increase the risk of hospitalization and death. So does lower education and lower income, the lowest incomes doubled the risk of death from COVID-19. Area estimates, where the model includes individual risks, show that high population density and a high percentage of foreign-born inhabitants increased the risk of hospitalization.Conclusions: Segregation and deprivation are public health issues elucidated by COVID-19. Neighborhood deprivation, prevalent in Stockholm, adds to individual risks and is associated with hospitalization and death. This finding is paramount for governments, agencies, and healthcare institutions interested in targeted interventions.
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| 7. |
- Bendtsen, Marcus, et al.
(författare)
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Effectiveness of a digital intervention versus alcohol information for online help-seekers in Sweden : a randomised controlled trial
- 2022
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Ingår i: BMC Medicine. - : BMC. - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ubiquity of Internet connectivity, and widespread unmet needs, requires investigations of digital interventions for people seeking help with their drinking. The objective of this study was to test the effectiveness of a digital alcohol intervention compared to existing online resources for help seekers. Methods: This parallel randomised controlled trial included 2129 risky drinkers with access to a mobile phone and aged 18 years or older. Randomised sub-studies investigated consent procedures and control group design. Simple computerised randomisation was used. Participants were aware of allocation after randomisation; research personnel were not. The digital intervention was designed around weekly monitoring of alcohol consumption followed by feedback and tools for behaviour change. Primary outcomes were total weekly consumption (TWC) and frequency of heavy episodic drinking (HED), measured 2 and 4 months post-randomisation. Results: Between 25/04/2019 and 26/11/2020, 2129 participants were randomised (intervention: 1063, control: 1066). Negative binomial regression was used to contrast groups, with both Bayesian and maximum likelihood inference. The posterior median incidence rate ratio (IRR) of TWC was 0.89 (95% CI = 0.81;0.99, 98.2% probability of effect, P-value = 0.033) at 2 months among 1557 participants and 0.77 (95% CI = 0.69;0.86, > 99.9% probability of effect, P-value < 0.001) at 4 months among 1429 participants. For HED, the IRR was 0.83 (95% CI = 0.75;0.93, > 99.9% probability of effect, P-value = 0.0009) at 2 months among 1548 participants and 0.71 (95% CI = 0.63;0.79, probability of effect > 99.9%, P-value < 0.0001) at 4 months among 1424 participants. Analyses with imputed data were not markedly different. Conclusions: A digital alcohol intervention produced self-reported behaviour change among online help seekers in the general population. The internal and external validity of this trial is strong, subject to carefully considered study limitations arguably inherent to trials of this nature. Limitations include higher than anticipated attrition to follow-up and lack of blinding.
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| 8. |
- Blomqvist, Jenny, et al.
(författare)
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Effects of a text messaging smoking cessation intervention amongst online help-seekers and primary health care visitors: findings from a randomised controlled trial
- 2023
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Ingår i: BMC Medicine. - : BMC. - 1741-7015. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Smoking continues to be a leading risk factor for several diseases globally. We hypothesised that an intervention delivered via text messages could help individuals who were looking to quit.Methods A two-arm, parallel-groups, randomised controlled trial was employed. Both groups received treatment as usual, with the intervention group also receiving a 12-week text messaging intervention. Participants were adult, weekly or more frequent smokers, recruited online and in primary health care centres. Research personnel were blinded, while participants were not. Primary outcomes were prolonged abstinence and point prevalence of abstinence, 3 and 6 months post-randomisation. All randomised participants were included in analyses.Results Between 18 September 2020 and 16 June 2022, we randomised 1012 participants (intervention: 505, control: 507). Outcome data was available for 67% (n = 682) of participants at 3 months and 64% (n = 643) at 6 months. At 3 months, the odds ratio (OR) of prolonged abstinence was 2.15 (95% compatibility interval [CoI] = 1.51; 3.06, probability of effect [POE] > 99.9%, p < 0.0001), and for point prevalence of abstinence, it was 1.70 (95% CoI = 1.18; 2.44, POE = 99.8%, p = 0.0034) in favour of the text messaging intervention. At 6 months, the OR of prolonged abstinence was 2.38 (95% CoI = 1.62; 3.57, POE > 99.9%, p = < 0.0001), and for point prevalence, it was 1.49 (95% CoI = 1.03; 2.14, POE = 98.3%, p = 0.0349) in favour of the text messaging intervention. Analyses with imputed data were not markedly different.Conclusions Amongst general population help-seekers-who on average had smoked for 25 years-access to a 12-week text messaging intervention produced higher rates of self-reported smoking abstinence in comparison to treatment as usual only. The intervention could be part of the societal response to the burden which smoking causes; however, findings are limited by risk of bias due to attrition, self-reported outcomes, and lack of blinding.
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| 9. |
- Breeur, Marie, et al.
(författare)
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Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition
- 2022
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations.Methods: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty.Results: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk.Conclusions: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
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| 10. |
- Bull, Caroline J., et al.
(författare)
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Adiposity, metabolites, and colorectal cancer risk : Mendelian randomization study
- 2020
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Ingår i: BMC Medicine. - : BMC. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. Methods We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models. Results In sex-specific MR analyses, higher BMI (per 4.2 kg/m(2)) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m(2)) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P <= 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles. Conclusions Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.
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