This register-based national cohort study of 206,900 individuals investigated whether prenatal exposure to small extra doses of vitamin D from fortified margarine prevented inflammatory bowel disease (IBD) later in life; whether the risk of IBD varied according to month or season of birth; and finally, whether there was an interaction between exposure to extra D vitamin and month or season of birth. Fortification of margarine with vitamin D was mandatory in Denmark from the mid-1930s until 1st June 1985, when it was abolished. Two entire birth cohorts, each including two years, were defined: one exposed and one unexposed to the fortification policy for the entire gestation. All individuals were followed for 30 years from the day of birth for an IBD diagnosis in Danish hospital registers. Logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Odds for IBD was lower among those exposed to extra D vitamin compared to those unexposed, OR = 0.87 (95% CI: 0.79; 0.95). No association with month or season of birth was found. However, estimates suggested that particularly children born during autumn may have benefitted from the effect of small extra doses of vitamin D. This is, to our knowledge, the first study to explore if prenatal exposure to vitamin D from fortification influenced the risk of IBD. Our results suggest that prenatal exposure to small amounts of extra vitamin D from food fortification may protect against the development of IBD before 30 years of age.

Few studies have examined the role of maternal diet in relation to development of coeliac disease (CD). In Denmark, cancellation of mandatory vitamin D fortification of margarine in June 1985 provided this opportunity. This study examined if season of birth or prenatal exposure to extra vitamin D from food fortification were associated with developing CD later in life. A strength of this study is the distinctly longer follow-up of patients (30 years). This register-based study has a semi-ecological design. Logistic regression analysis was used to estimate odds ratios and to calculate 95% confidence intervals. The odds ratio for developing CD was 0.81 (95% CI 0.66; 1.00 p = 0.054), comparing those with fetal exposure to mandatory vitamin D fortification policy of margarine to those without after adjusting for gender and season of birth. There was a statistically significant season effect particularly for children born in autumn (OR 1.6 95% CI 1.16; 2.21) and born in summer (OR 1.5 95% CI 1.1; 2.1) when compared to children born in winter. Although this study did not find evidence to support the premise that prenatal exposure to small extra amounts of vitamin D from a mandatory food fortification policy lowered risk of developing CD, the small number of CD cases and observed association between season of birth and CD suggest that environmental exposure ought to be further explored.

By utilizing historical changes in Danish legislation related to mandatory vitamin D fortification of margarine, which was implemented in the mid 1930s and abruptly abandoned in June 1985, the studies in the D-tect project investigated the effects of vitamin D on health outcomes in individuals, who during gestation were exposed or unexposed to extra vitamin D from fortified margarine. This paper reviews and narratively summarizes the analytic approaches alongside the results of the societal fortification experiment studies from the D-tect project and addresses the challenges in designing societal experiment studies and evaluating their results. The latter are discussed as lessons learned that may be useful for designers of similar studies, expected to be extensively utilized while researching the health consequences of the COVID-19 pandemic by comparing individuals born before and after the epidemic. In the D-tect project, 16 articles based on the societal fortification experiment were published analyzing 10 different outcomes and using different statistical approaches. Lessons learned included the detail of the analysis of the historical information on the exposure, availability and validity of the outcome data, variety of analytical approaches, and specifics concerning vitamin D effect evaluation, such as consideration of the influence of sunshine or season. In conclusion, the D-tect project clearly demonstrated the cost-effectiveness and research potential of natural- or societal-experiment-based studies.

IntroductionMore than 10% of the population worldwide is affected by chronic kidney disease (CKD). Despite many promising indications regarding the use of mHealth education for patients with CKD, there is still little evidence regarding the feasibility, effectiveness outcomes and outcome measures. Therefore, we will conduct a scoping review to examine the currently available evidence on mHealth education for patients with CKD and, thus, explore the existing evidence regarding feasibility, effectiveness outcomes and outcome measures, patient and/or provider perception and implementation challenges.Methods and analysisA scoping review will be conducted in accordance with Joanna Briggs Institute Manual for Evidence Synthesis chapter on scoping reviews.MEDLINE, Embase, CINAHL and PsycINFO will be searched. The search strategy will consist of blocks, which have been adopted and modified from former Cochrane reviews. Two independent reviewers will screen studies. Characteristics of the included studies, both quantitative and qualitative, will be reported using quantitative descriptive statistics. Quantitative results will be grouped by objectives (feasibility, effectiveness outcomes and outcome measures, patient perception and implementation challenges), types of intervention and characteristics of participants. Qualitative results will be organised into categories using an iterative process, as suggested by Pollock et al.Ethics and disseminationAs this scoping review does not involve primary data collection, ethical permission is unnecessary. Results of the scoping review will be published in an international peer-reviewed scientific journal.Trial registration numberOpen Science Framework (https://osf.io/gxkeh/).

Purpose After thyroid surgery, the overriding concern is the risk of post-thyroid bleeding (PTB). This systematic review and meta-analysis aimed to assess the safety of hemithyroidectomy in an outpatient setting compared to an inpatient setting. The objectives were to (1) find the proportion of PTB in patients scheduled for outpatient hemithyroidectomy, (2) examine if outpatient hemithyroidectomy is clinically safe compared to an inpatient setting and (3) evaluate which selection criteria are most relevant for hemithyroidectomy in an outpatient setting. Methods A systematic review was conducted using the following databases: MEDLINE (Ovid), EMBASE (Ovid) and the Cochrane Library from inception until September 2021. We included studies reporting on PTB of patients after hemithyroidectomy in an outpatient setting. The risk of bias was assessed using the Newcastle-Ottawa tool. The results were synthesised using Bayesian meta-analysis. Certainty in evidence was assessed using the GRADE approach. Results This review included 11 cohort studies and 9 descriptive studies reporting solely on outpatients resulting in a total of 46,866 patients. PTB was experienced by 58 of the 9025 outpatients (0.6%) and 415 of the 37,841 inpatients (1.1%). There was no difference between the PTB rate of outpatients and inpatients (RR 0.715 CrI [0.396–1.243]). The certainty of the evidence was very low due to the high risk of bias. Conclusion The risk of PTB in an outpatient setting is very low, and outpatient hemithyroidectomy should be considered clinically safe. The most relevant selection criteria to consider in outpatient hemithyroidectomy are (1) relevant comorbidities and (2) psycho/-social factors.

ObjectiveBreast cancer is the most common cancer diagnosis among women. The acute crisis and uncertainty that often follow diagnosis put the family at risk of exhaustion and dysfunction. Adolescents have been identified as a particularly vulnerable group of relatives. To investigate how to prevent distress in this group, we systematically reviewed research on adolescents' (11–21 years) needs for information and psycho‐social support during their mothers' breast cancer trajectory.MethodSystematic searches were conducted in five bibliometric databases. Peer‐reviewed, original research of adolescents aged 11–21 with a mother diagnosed with breast cancer was included. Two researchers conducted screening, quality assessment, and data extraction independently. Thematic synthesis was applied to the included studies.ResultsA total of 8066 studies were screened, and five quantitative and six qualitative studies were included. The results indicated that adolescents' information and psycho‐social support needs were poorly met. Many were reluctant to share feelings with family and peers and experienced abandonment during the crisis. Adolescents who were not well informed experienced distress. Poor family functioning increased the level of adolescents' distress.ConclusionsDespite limitations regarding heterogeneity among the studies, eligibility criteria, and quality assessment, this review provides clear clinical implications. Encounter groups may support adolescents during their mother's breast cancer trajectory. Furthermore, healthcare professionals could provide more indirect support to adolescents by providing support and clearer guidelines to parents. Finally, adolescents from poor‐functioning families need extra attention.

Introduction Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disease that can affect the entire digestive tract. Approximately 1% of the Danish population has IBD today. Both the incidence and prevalence of IBD are increasing globally, but the etiology of IBD is still not fully understood. Some, but not all studies find that vitamin D has both protective and therapeutic effects on IBD. To our knowledge, no other study has investigated prenatal exposure to extra vitamin D from either fortified food, diet or supplements in relation to IBD. The aim of this study was to investigate whether a small extra dose of vitamin D from fortification during gestation, was associated with a lower risk of developing IBD in the offspring. Methods In 1985 mandatory fortification of margarine with vitamin D in Denmark was canceled. To investigate the effect of this policy change we selected all individuals from 2 full year birth cohorts before and after the termination of the mandatory fortification. All individuals were followed for 30 years. By merging data from the Medical Birth Registry with the Danish National Patient Registry, we identified individuals with IBD. Results 217,249 individuals were included in the analysis. 875 among the exposed and 1102 among the unexposed fulfilled the criteria for being diagnosed with IBD. A lower odds ratio OR = 0.867 (95% CI: 0.792;0.947) for IBD was observed among those who had been exposed to extra vitamin D from fortified margarine during gestation, compared to those who had not been exposed. The analysis was adjusted for sex and season of birth, but results were essentially similar before and after this adjustment. Conclusions This study shows, that a small extra dose of vitamin D from fortified margarine during gestation may lower the risk of developing IBD in the offspring, until the age of 30. If these results can be replicated, fortification with vitamin D could be recommended to prevent IBD on a public level. Key messages Prenatal exposure of vitamin D from fortified food could lower the risk of IBD later in life. Fortification with vitamin D even at a relatively low level could have public health benefits.

Background Inflammatory bowel diseases (IBDs) are often associated with high healthcare utilisation. This systematic review aimed to summarize what is known about the impact of sex, income, and education on the risk of bowel surgery, hospitalization and use of corticosteroids and biologics among patients with IBD. Methods We used EMBASE, MEDLINE, CINAHL, and Web of Science to perform a systematic literature search. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis for the impact of sex on risk of surgery and hospitalization. In addition, we performed subgroup analyses of the effect of IBD type (Crohn’s disease or ulcerative colitis), children or adults, and country. Finally, meta-regression was undertaken for the year of publication. Results In total, 59 studies were included. In the meta-analysis, male sex was associated with an increased risk of bowel surgery in UC patients (HR: 1.78, 95% CI: 1.16;2.72) and an increased risk of hospitalization in CD patients (OR: 1.42, 95% CI: 1.28;1.58). In 6 of 6 studies, female patients had lower adherence to biologics, whereas 9 of 10 studies reported no significant sex-based difference in use of corticosteroids. The evidence of the impact of income and education on all four outcomes was sparse and pointed in different directions. The substantial heterogeneity between studies was explained, in part, by differences in IBD type, age and country. Conclusions Population-based observational studies have revealed that sex influence the surgery rate and risk of hospitalization among IBD patients with more men having surgeries and hospitalizations than women, whereas female patients appear to have statistically significantly lower adherence to biologics compared to male patients. Thus, clinicians should not underestimate the impact of sex on patient outcomes. Evidence for income- and education based differences remains sparse. Systematic review registration: PROSPERO Registration ID: CRD42022315788.