Effects on Pediatric Cancer Survivors: The FAMily-Oriented Support (FAMOS) Randomized Controlled Trial.

OBJECTIVE: To examine as secondary analyses the effect the FAMily-Oriented Support (FAMOS) family therapy program on reducing parent-reported medical traumatic stress in the sub-sample of pediatric cancer survivors, age 2-5 years. METHODS: The FAMOS study was a national multicenter randomized controlled trial with all four pediatric oncology departments in Denmark (Clinicaltrials.gov [NCT02200731]). Families were randomized in parallel design (1:1) to intervention or usual care. The FAMOS program includes seven home-based psychotherapeutic sessions and is based on family systems therapy to address the individuals in the family system using cognitive behavioral, problem-solving and goal-setting techniques. Questionnaires were completed by parents at baseline, 6, and 12 months. In linear mixed-effects models, the effect of FAMOS on reducing children's trauma-related behavior after 6 and 12 months was examined in 62 children (31 in the intervention and 29 in the control group, respectively). It was also examined if a trauma-related behavior effect was mediated through reduced symptoms of depression in mothers and fathers, respectively. RESULTS: On average, children in the intervention group experienced significantly larger decreases in trauma-related behaviors at 6 and 12 months than the control group (predicted mean difference -3.89, p = .02 and -6.24, p = .003, respectively). The effect on trauma-related behavior was partly mediated through reduced symptoms of depression in mothers, but not fathers. CONCLUSIONS: Adding to previously reported positive effects of the FAMOS intervention on parents' symptoms of post-traumatic stress and depression, significant improvements were found in young children's trauma related-behavior. Further research is needed to develop therapy for children with cancer.

Use of hypnotics among women diagnosed with cervical cancer - A population-based cohort study.

OBJECTIVE: Previous studies suggest that sleeping problems are frequent after cervical cancer. However, the evidence on the use of hypnotics is sparse. We investigated if women diagnosed with cervical cancer have an increased risk of using hypnotics and identified risk factors for prolonged use. METHODS: In this nationwide register-based cohort study, 4264 women diagnosed with cervical cancer from 1997 to 2013 and 36,632 cancer-free women were followed in registers until 2016. Prolonged use of hypnotics was defined as more than three prescriptions with no more than three months in between. Data were analysed using Cox proportional hazards regression models and multistate Markov models separately for women with localized and advanced cervical cancer. RESULTS: The rate of first use of hypnotics was substantially increased during the first year after cervical cancer diagnosis compared to cancer-free women (HRlocalized 4.4, 95% CI 3.9-5.1; HRadvanced 8.9, 95% CI 7.5-10.6) and remained markedly increased for up to five years after diagnosis. Dependent on stage of disease and age, 1.4 to 4.7 excess women per 100 with cervical cancer were prolonged users of hypnotics compared to cancer-free women one year after diagnosis. Risk factors for prolonged use of hypnotics were higher age, short education, previous use of antidepressants or anxiolytics, and advanced disease. CONCLUSIONS: Women diagnosed with cervical cancer are at increased risk of prolonged use of hypnotics. For the majority, treatment with hypnotics is initiated within the first year after cancer diagnosis, but the rate of first use is increased for up to five years.

Risk of depression after diagnostic prostate cancer workup - A nationwide, registry-based study.

OBJECTIVE: To compare the risk of depression after diagnostic workup for prostate cancer (PCa), regardless of the histopathologic outcome, with that of a cancer-free population. METHODS: A nationwide cohort of Danish men who had a prostatic biopsy sample in 1998-2011 was identified from the Danish Prostate Cancer Registry and compared to an age-matched cohort from the background population. Men with other cancers, major psychiatric disorder, or prior use of antidepressants were excluded. The risk of depression defined as hospital contact for depression or prescription for antidepressants was determined from cumulative incidence functions and multivariate Cox regression models. RESULTS: Of 54,766 men who underwent diagnostic workup for PCa, benign results were found for 21,418 and PCa was diagnosed in 33,347. During up to 18 years of follow-up, the adjusted hazard of depression was higher in men with PCa than in the background population, with the highest risk in the two years after diagnosis (hazard ratio (HR) 2.77, 95% CI 2.66-2.87). Comorbidity and lowest or highest income were significant risk factors for depression and the cumulative incidence was substantially higher in men with metastatic or high-risk disease. In men with benign histopathology the HR for depression was 1.22 (95% CI 1.14-1.31) in the first two years but no different from the background population after that. CONCLUSIONS: Diagnostic workup for PCa is associated with an increased risk of depression, mainly among men with a diagnosis of PCa. Clinicians should be aware of depressive symptoms in prostate cancer patients.

Effects of substitution dietary guidelines targeted at prevention of IHD on dietary intake and risk factors in middle-aged Danish adults: the Diet and Prevention of Ischemic Heart Disease: a Translational Approach (DIPI) randomised controlled trial.

The objective was to investigate the effects of substitution (SUB) dietary guidelines (DG) targeted at the prevention of IHD on dietary intake and IHD risk factors in Danish adults with minimum one self-assessed IHD risk factor. A 6-month single-blinded parallel randomised controlled trial with a follow-up at month 12 included 219 subjects (median age 51 years, 59 % female, 73 % overweight or obese) randomised into an SUB DG, an official (OFF) DG or a control group following their habitual diet (HAB). Participants in the DG intervention groups received bi-weekly reminders of their DG and recipes for dishes and the HAB group received a greeting. Dietary intake and fasting blood, anthropometric and blood pressure measurements were obtained at baseline, month 6 and month 12. Linear regression analyses were applied. At month 6, when compared with the HAB, the SUB had a greater impact on the extent of dietary changes with increased intake of whole grains, dietary fibre and low fibre vegetables compared with the OFF DG, and both DG groups had similar decreased percentage of energy (E%) intake from SFA. The extent of dietary changes was similar at month 12. No overall significant changes from baseline were found in blood pressure, anthropometrics and IHD risk markers. In conclusion, both SUB and OFF DG resulted in cardioprotective dietary changes. However, neither the SUB nor the OFF DG resulted in any overall effects on the selected intermediate risk factors for IHD.

Home-based cognitive behavioural therapy for families of young children with cancer (FAMOS): A nationwide randomised controlled trial.

INTRODUCTION: Evidence-based knowledge is needed to reduce psychological symptoms in families of young children with cancer after treatment ends. OBJECTIVE: To evaluate the effect of a psychotherapeutic intervention, FAMily-Oriented Support (FAMOS) on parents of young children after cancer treatment. METHODS: All families of children aged 0-6 years who had been treated for cancer at one of the four paediatric oncology departments in Denmark were invited to participate after ending intensive medical treatment. The families were randomly assigned 1:1 to up to seven sessions of FAMOS, a cognitive-behavioural manualised home intervention, for 6 months or to usual psychosocial care. The primary outcome was parents' symptoms of posttraumatic stress disorder (PTSD) at 6 and 12 months after enrolment. The secondary outcomes were parents' symptoms of depression and anxiety. RESULTS: We enrolled 109 families (204 parents). Parents in the intervention group did not show a statistically significant decrease in symptoms of PTSD as compared with the control group at 6 months (predicted mean difference, -0.10; 95% confidence interval [CI] -0.19, 0.01), but a statistically significant decrease was seen at 12 months (predicted mean difference, -0.15; 95% CI -0.28, -0.02), and they had significantly lower symptoms of depression at both 6 and 12 months. Differences in reductions in symptoms of anxiety were not statistically significant. CONCLUSIONS: The FAMOS intervention reduced parents' symptoms of PTSD and depression. Next step is to also report on psychological effects in the children and siblings (clinicaltrials.gov: NCT02200731).

The psychological symptom burden in partners of pancreatic cancer patients: a population-based cohort study.

PURPOSE: Pancreatic cancer (PC) has high morbidity and mortality and is stressful for patients and their partners. We investigated the psychological symptom burden in partners of PC patients. METHODS: We followed 5774 partners of PC patients diagnosed from 2000 to 2016 up for first redeemed prescriptions of antidepressants or hospital admission, anxiolytics, and hypnotics as proxies for clinical depression, anxiety, and insomnia and compared them with 59,099 partners of cancer-free spouses. Data were analysed using Cox regression and multistate Markov models. RESULTS: The cumulative incidence proportion of first depression was higher in partners of PC patients compared to comparisons. The highest adjusted HR of first depression was seen the first year after diagnosis (HR 3.2 (95% CI: 2.9; 3.7)). Educational level, chronic morbidity, and bereavement status were associated with an increased risk of first depression. There was a significantly higher first acute use (1 prescription only) of both anxiolytics and hypnotics and chronic use (3+ prescriptions) of hypnotics in partners of PC patients than in comparisons. CONCLUSION: Being a partner to a PC patient carries a substantial psychological symptom burden and increases the risk for first depression and anxiolytic use and long-term use of hypnotics. Attention should be given to the psychological symptom burden of partners of PC patients, as this may pose a barrier for the optimal informal care and support of the PC patient, as well as a risk for non-optimal management of symptoms in the partner.

Effect of progressive resistance training on persistent pain after axillary dissection in breast cancer: a randomized controlled trial.

PURPOSE: Persistent pain is a known challenge among breast cancer survivors. In secondary analyses of a randomized controlled trial, we examined the effect of progressive resistance training on persistent pain in the post-operative year in women treated for breast cancer with axillary lymph node dissection. METHODS: We randomized 158 women after BC surgery with Axillary Lymph Node Dissection (ALND) (1:1) to usual care or a 1-year, supervised and self-administered, progressive resistance training intervention initiated 3 weeks after surgery. A questionnaire at baseline, 20 weeks and 12 months assessed the intensity and frequency of pain, neuropathic pain and influence of pain on aspects of daily life. We analysed the effect using linear mixed models and multinomial logistic regression models for repeated measures. RESULTS: A high percentage of participants experienced baseline pain (85% and 83% in the control and intervention groups respectively) and by the 12 month assessment these numbers were more than halved. A high proportion of participants also experienced neuropathic pain (88% and 89% in control and intervention group respectively), a finding that was stable throughout the study period. The effect on intensity of pain indicators favoured the exercise group, although most estimates did not reach statistical significance, with differences being small. CONCLUSION: For women who had BC surgery with ALND, our progressive resistance training intervention conferred no benefit over usual care in reducing pain. Importantly, it did not increase the risk of pain both in the short and long term rehabilitative phase.

Clinical characteristics and quality of life, depression, and anxiety in adults with neurofibromatosis type 1: A nationwide study.

Neurofibromatosis type 1 (NF1) is a genetic condition characterized by numerous somatic manifestations. The psychosocial burden in adults has rarely been studied. We examined the prevalence of self-reported impairment of quality of life (QoL), symptoms of anxiety and depression and need for support, associated with disease severity and visibility. We conducted a nationwide cross-sectional study of all 467 adults with NF1 diagnosed between 1977 and 2016 at one of the two national centers for rare diseases in Denmark. A total of 244 (56% response rate) completed a questionnaire that included standard measures of QoL, symptoms of depression and anxiety, indicators of disease-related severity, visibility, and need for professional support. Associations between disease severity and visibility and psychosocial burden were analyzed in descriptive and multivariate models. We observed impaired QoL (mean = 81.3; 95% CI, 76.2; 86.4); 19% reported symptoms of depression (mean = 5.7; SD = 5.4), and 15% reported anxiety (mean = 5.1; SD = 5.2) at a clinical level. Adults with NF1 also reported requiring professional support for physical, psychological, and work-related problems. Disease severity and (partly) visibility were significantly (p < .0001) associated with psychosocial well-being and a requirement for support. This study provides new understanding of the factors associated with impaired QoL, indicating that follow-up care should be optimized into adult life.

Increased psychological symptom burden in patients with pancreatic cancer: A population-based cohort study.

BACKGROUND/OBJECTIVE: To investigate the psychological symptom burden in patients with pancreatic cancer. METHODS: We used Danish population-based registries to identify 10,793 pancreatic cancer patients and 109,238 age and gender matched cancer-free comparison persons between the years 2000-2016. The cohorts were followed up to five years for first prescription for antidepressants, anxiolytics or hypnotics as proxies for the psychological symptom burden of depression, anxiety or insomnia. Cumulated incidence proportions were analysed using the pseudo-value approach and hazards were estimated with Cox regression models adjusted for potential confounders. RESULTS: The highest HR for first antidepressant use was seen in the first six months after diagnosis (HR 8.73 (95% CI: 7.57; 10.06)). Within the first two years the overall estimated cumulated probability of 12.9% (95% CI: 12%; 13.8%) in pancreatic cancer patients, and 4.6% (95% CI: 4.5%; 4.8%) in comparisons, and 20.4% and 31.4% patients received first prescription of anxiolytics or hypnotics, respectively. We found no difference in HRs of first antidepressant by gender, year of diagnosis, cohabitation, education or comorbidity in the patient cohort, however younger age (<59 years) was associated with depression. CONCLUSIONS: Pancreatic cancer patients are at risk for first antidepressant, anxiolytic and hypnotic use up to five years after diagnosis. Patients younger than 59 years, newly diagnosed with advanced pancreatic cancer, and not treated with surgery were more likely to have first antidepressant use. The study calls for interventions to reduce the psychological burden in advanced pancreatic cancer patients which may improve quality of life and survival.

Neurologic disorders in long-term survivors of neuroblastoma - a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) research program.

Background: Neuroblastoma is the commonest extracranial solid tumor of childhood, yet rare, and with poor survival before 1990, especially for high-risk disease; thus, information on late effects is sparse. With great advances in cancer treatment, survival has reached 80% in the Nordic countries. The aim of the study was to investigate the risk of developing neurologic disorders after neuroblastoma.Material and methods: Through population-based cancer registries of four Nordic countries we identified 654 5-year survivors of neuroblastoma (diagnosed 1959-2008) and 133,668 matched population comparisons. We grouped neurologic diagnoses from national hospital registries into 11 main diagnostic categories and 56 disease-specific sub-categories and calculated relative risks (RRs), absolute excess risks (AERs), cumulative incidence and mean cumulative count (MCC). Information on cancer treatment was available for 49% of survivors.Results: A hospital contact for a neurologic disorder was observed in 181 survivors 5 years or more from cancer diagnosis with 59 expected, yielding a RR of 3.1 (95% CI 2.7-3.6) and an AER of 16 per 1,000 person-years (95% CI 12-19). The most frequent disorders included epilepsy, paralytic syndromes, diseases of the eyes and ears and hearing loss. The cumulative incidence of any neurologic disorder was 31% in survivors 20 years after cancer diagnosis with a MCC of 0.5 unique diagnoses. All risks were highest in survivors of high-risk neuroblastoma.Conclusion: Neuroblastoma survivors represent a population with a high risk of developing neurologic disorders. Our results should contribute to improving health care planning and underscores the need for systematic follow-up care of this vulnerable group of survivors.

Progressive resistance training to prevent arm lymphedema in the first year after breast cancer surgery: Results of a randomized controlled trial.

BACKGROUND: Existing research suggests that progressive resistance training (PRT) after breast cancer (BC) surgery is safe, but the preventive effect on arm lymphedema has yet to be determined. METHODS: Women aged 18 to 75 years who were undergoing BC surgery with axillary lymph node dissection were eligible for the study. Recruited on the day of surgery, participants were allocated to intervention or usual care by computer randomization. The intervention consisted of PRT 3 times per week: in the first 20 weeks as a supervised group exercise and in the last 30 weeks as a self-administered exercise. The primary outcome was arm lymphedema, which was defined as a >3% increase in the interlimb volume difference by water displacement. Measurements were made at the baseline and at a 12-month follow-up by physiotherapists blinded to group allocation. Analyses of effects included t tests and regression models; missing data were addressed by multiple imputation. RESULTS: Among the 158 randomized women, no mean group difference was found in arm volume (0.3%; 95% confidence interval, -1.7% to 2.3%) or lymphedema incidence (adjusted odds ratio, 1.2; 95% confidence interval, 0.5-2.8). None of the participants exited the program because of adverse events. CONCLUSIONS: This study provides no evidence that PRT can prevent arm lymphedema in the first year after BC, but the results corroborate the importance and safety of resistance training for patients, including women at high risk for lymphedema.

Modelling of adequate and safe vitamin D intake in Danish women using different fortification and supplementation scenarios to inform fortification policies.

PURPOSE: Fortification of foods with vitamin D may be a population-based solution to low vitamin D intake. We performed modelling of vitamin D from diet, fortified foods and supplements in a population of Danish women 18-50 years, a risk group of vitamin D deficiency, to inform fortification policies on safe and adequate levels. METHODS: Based on individual habitual dietary vitamin D intake of female participants from the Danish National Survey of Dietary Habits and Physical Activity (DANSDA) (n = 855), we performed graded intake modelling to predict the intake in six scenarios increasing the vitamin D intake from a habitual diet without fish to habitual diet including fish, fortified foods and supplements (40/80 µg). Four different foods were used as potential foods to fortify with vitamin D. RESULTS: The vitamin D intake was below the Average Requirement (AR) of 7.5 µg/day for 88% of the assessed women. Safe levels of intake (< 100 µg/day) were observed after adding four different fortified foods (plain yoghurt, cheese, eggs and crisp-bread) contributing with a total of 20 µg/day and a vitamin D supplement of 40 µg/day to the habitual diet. Consumption of fish, fortified foods and a vitamin D supplement of 80 µg resulted in intakes above the Tolerable Upper Intake Level (UL) < 100 µg/day. CONCLUSIONS: In a Danish female population with a low vitamin D intake, low-dose fortification of different foods with vitamin D may be an effective and safe population-based approach.

Effect of vitamin D fortified foods on bone markers and muscle strength in women of Pakistani and Danish origin living in Denmark: a randomised controlled trial.

BACKGROUND: Deficient and insufficient vitamin D status (defined as serum 25(OH)D < 30 nmol/L and > 50 nmol/L) is prevalent worldwide and associated with decreased muscle strength and poor bone health. We aimed to investigate the effect of vitamin D fortification on bone markers and muscle strength among younger adult women at risk of vitamin D deficiency. METHODS: A 12-week randomised double-blinded placebo-controlled winter intervention trial, providing 30 µg vitamin D3/day through fortified yoghurt, cheese, eggs and crisp-bread or similar placebo products. Participants were 143 women of Danish and Pakistani origin 18-50 years of age, living in Denmark, randomised into four groups stratified by ethnicity. Serum 25-hydroxyvitamin D (25(OH)D) by LC-MS/MS and the secondary endpoints: four specific bone markers (osteocalcin (OC), Bone specific Alkaline Phosphatase (BALP), Procollagen type 1 amino-terminal propeptide (P1NP), C-terminal crosslinked telopeptide of type 1 collagen (CTX)) and three muscle strength measures (handgrip, knee extension strength, chair-standing), were assessed using one-way ANOVA, Tukey HSD and subsequent linear ANCOVA models, adjusted for relevant covariates. RESULTS: Significantly increased serum 25(OH)D concentration from 53.3 (17) to 77.8 (14) nmol/L and from 44.5 (21) to 54.7 (18) nmol/L among Danish and Pakistani women in the fortified groups, respectively (P <  0.05). The bone turnover markers OC, BALP, P1NP and CTX did not change significantly. Muscle strength by handgrip, knee extension and chair-standing test did not change significantly following the intervention. CONCLUSIONS: Consumption of vitamin D fortified foods for 12 weeks did not result in significant changes of the bone turnover markers OC, BALP, P1NP and CTX. Muscle strength measured as hand grip strength, knee extension strength and chair-standing did not change significantly following the intervention.

Optimistic and pessimistic self-assessment of own diets is associated with age, self-rated health and weight status in Danish adults.

The aim of this study was to analyse concordance between Danish adults' recorded diet quality and their own assessment of the healthiness and to examine socio-demographic, health and behavioural characteristics associated with an optimistic or pessimistic self-assessment. Data were derived from The Danish National Survey of Diet and Physical Activity 2011-2013 and included a random sample of 3014 adults (18-75 y). Diet quality was evaluated on the basis of seven-day pre-coded food diaries and categorised 'unhealthy', 'somewhat healthy' and 'healthy'. Self-assessment of the healthiness of own diets was registered via personal interviews and categorised healthy enough 'to a high degree', 'to some degree' or 'not at all/only partly'. Highly and somewhat optimistic self-assessment, respectively, were defined as assessing own diets as healthy enough to a high degree or to some degree while having unhealthy diets. Highly and somewhat pessimistic self-assessment, respectively, were defined as assessing own diets as not healthy enough or healthy enough to some degree while having healthy diets. Multiple logistic regression models were used to examine characteristics associated with optimistic and pessimistic self-assessments, respectively. Among individuals with unhealthy diets, 13% were highly optimistic and 42% somewhat optimistic about the healthiness of their diets. Among individuals with healthy diets, 14% were highly pessimistic and 51% somewhat pessimistic about the healthiness of their diets. Highly optimistic self-assessment was associated with increasing age, excellent self-rated health, normal weight and a moderate activity level. Highly pessimistic self-assessment was associated with decreasing age, good self-rated health and being obese. The findings indicate that people seem to use personal health characteristics as important references when assessing the healthiness of their diets.

Accuracy of self-reported intake of signature foods in a school meal intervention study: comparison between control and intervention period.

Bias in self-reported dietary intake is important when evaluating the effect of dietary interventions, particularly for intervention foods. However, few have investigated this in children, and none have investigated the reporting accuracy of fish intake in children using biomarkers. In a Danish school meal study, 8- to 11-year-old children (n 834) were served the New Nordic Diet (NND) for lunch. The present study examined the accuracy of self-reported intake of signature foods (berries, cabbage, root vegetables, legumes, herbs, potatoes, wild plants, mushrooms, nuts and fish) characterising the NND. Children, assisted by parents, self-reported their diet in a Web-based Dietary Assessment Software for Children during the intervention and control (packed lunch) periods. The reported fish intake by children was compared with their ranking according to fasting whole-blood EPA and DHA concentration and weight percentage using the Spearman correlations and cross-classification. Direct observation of school lunch intake (n 193) was used to score the accuracy of food-reporting as matches, intrusions, omissions and faults. The reporting of all lunch foods had higher percentage of matches compared with the reporting of signature foods in both periods, and the accuracy was higher during the control period compared with the intervention period. Both Spearman's rank correlations and linear mixed models demonstrated positive associations between EPA+DHA and reported fish intake. The direct observations showed that both reported and real intake of signature foods did increase during the intervention period. In conclusion, the self-reported data represented a true increase in the intake of signature foods and can be used to examine dietary intervention effects.

Reduction in pedometer-determined physical activity in the adult Danish population from 2007 to 2012.

AIMS: To examine the development in pedometer-determined physical activity from 2007-2008 to 2011-2012 in the adult Danish population. METHODS: The study population comprised two random samples of 18-75-year-old individuals who took part in cross-sectional studies in 2007-2008 (n=224) and 2011-2012 (n=1515). Pedometer data (sealed Yamax SW 200) were obtained for seven consecutive days. Data for 1624 participants (48.2% men) were included in the analysis. An overall step-defined activity level was examined based on a graduated step index (sedentary, low active, somewhat active, active, highly active). The pedometer-determined outcomes were analysed using regression models. RESULTS: A borderline significant decline (p=0.077) from 8788 to 8341 steps/day (-446 (95% confidence intervals -50, 943)) was found between 2007-2008 and 2011-2012. Furthermore, a 23.7% (95% confidence intervals -41.7%, -0.1%) lower overall step-defined activity level was observed in 2011-2012 compared to 2007-2008. These changes were primarily due to a reduced level of activity among women. The proportion of individuals taking ⩾10,000 steps/day decreased non-significantly from 34.8% to 29.3%, whereas the proportion taking <5000 steps/day did not differ between survey periods. CONCLUSIONS: This nationally representative survey suggests an overall reduction in the physical activity level among Danish adults. The reduction was due to a shift in the population distribution from higher to lower levels of activity. If this shift is true, it is worrying from a public health perspective. Our study result needs, however, to be confirmed by other population studies.

Short communication: artificial ultraviolet B light exposure increases vitamin D levels in cow plasma and milk.

The number of dairy cows without access to pasture or sunlight is increasing; therefore, the content of vitamin D in dairy products is decreasing. Ultimately, declining vitamin D levels in dairy products will mean that dairy products are a negligible source of natural vitamin D for humans. We tested the ability of a specially designed UVB lamp to enhance the vitamin D3 content in milk from dairy cows housed indoors. This study included 16 cows divided into 4 groups. Each group was exposed daily to artificial UVB light simulating 1, 2, 3, or 4 h of summer sun at 56°N for 24 d, and the group with simulated exposure to 2 h of summer sun daily continued to be monitored for 73 d. We found a significant increase in 25-hydroxyvitamin D3 (25OHD3) levels in plasma as well as vitamin D3 and 25OHD3 levels in milk after daily exposure for 24 d in all treatment groups. Extending daily exposure to artificial UVB light to 73 d did not lead to an increase of vitamin D3 or 25OHD3 level in the milk. In conclusion, the change in production facilities for dairy cows providing cows with no access to pasture and sunlight causes a decrease of vitamin D levels in dairy products. This decrease may be prevented by exposing cows to artificial UVB light in the stable.

Risk of cardiovascular disease in family members of young sudden cardiac death victims.

AIMS: Descriptive and genetic studies suggest that relatives of sudden cardiac death (SCD) victims have an increased risk of several cardiovascular diseases (CVDs). Given the severe consequences of undiagnosed CVD and the availability of effective treatment, the potential for prevention in this group is enormous if they do have an increased CVD risk. This nationwide prospective population-based cohort study described the risk of CVDs in relatives of young SCD victims, compared with the general population. METHODS AND RESULTS: All SCD victims aged 1-35 years in Denmark, 2000-2006, were identified (n = 470), along with their first- and second-degree relatives (n = 3073). We compared the incidence of CVD in those relatives with that in the background population using standardized incidence ratios (SIRs). The observed number of CVDs over 11 years of follow-up was 292, compared with 219 expected based on national rates [SIR 1.33, 95% confidence interval (CI) 1.19-1.50]. Risks varied significantly with age; the SIR for those <35 years was 3.53 (95% CI 2.65-4.69), compared with SIRs of 1.59 (95% CI 1.35-1.89) and 0.91 (95% CI 0.75-1.10) for those aged 35-60 years or >60 years, respectively (P(homogeneity) < 0.0001). For first-degree relatives <35 years, SIRs for ischaemic heart disease, cardiomyopathy, and ventricular arrhythmia were 5.99 (95% CI 1.95-0.13.98), 17.91 (95% CI 4.88-45.87), and 19.15 (95% CI 7.70-39.45), respectively. CONCLUSION: CVDs co-aggregated significantly with SCD in families, with young first-degree relatives at greatest risk. Results clearly indicate that family members of young SCD victims should be offered comprehensive and systematic screening, with focus on the youngest relatives.

Antipsychotic exposure and infection risk in people with schizophrenia spectrum disorders during the COVID-19 pandemic: a Danish nationwide registry study.

BACKGROUND: Infection risk and mortality are increased in schizophrenia spectrum disorders, which was corroborated during the COVID-19 pandemic. However, evidence is lacking regarding the additional impact of antipsychotic drugs, and the highly debated safety of clozapine treatment during large-scale infection outbreaks. Therefore, we aimed to investigate risk of COVID-19 and non-COVID respiratory infections during exposure to antipsychotics. METHODS: We used several nationwide Danish registers (National Prescription Registry, National Hospital Registry, Psychiatric Research Register, Microbiology Database, Vaccination Registry, Cause of Death Registry, and Database for Labour market Research) to investigate all individuals aged 18 years or older with a schizophrenia spectrum disorder (ICD-10: F20-F29) living in Denmark between Jan 1 and March 1, 2020. Antipsychotic exposure groups were defined as prevalent-users and incident-users. The full observation period was March 1, 2020 to Dec 31, 2021. Antipsychotic exposure was defined in a time-varying manner and compared with non-exposure. Risk was calculated for mild infection outcomes (positive SARS-CoV-2 PCR and anti-infective drug prescriptions) and severe infection outcomes (hospitalisation and death) related to COVID-19 and non-COVID-19 respiratory infections. Outcomes were adjusted for demographics, socio-economic factors, and comorbidity. FINDINGS: Of 85 083 individuals (44 293 men [52·1%] and 40 790 women [47·9%], median age 45·8 years [IQR 31·1-60·2]) with pre-existing schizophrenia spectrum disorders, 30 984 had antipsychotic exposure periods. Ethnicity data were not available. During antipsychotic exposure compared with non-exposed periods, assessing mild infection outcomes, risk of a positive SARS-CoV-2 test was decreased (hazard ratio 0·91 [95% CI 0·85-0·97]) and risk of redeeming an anti-infective drug was not statistically significantly different (1·01 [0·97-1·06]). For severe infection outcomes, COVID-19-related hospitalisation risk was increased (1·28 [1·07-1·52]) although COVID-19-related death was not statistically significantly increased (1·24 [0·82-1·86]). For non-COVID-19 respiratory infections, risk was increased both for hospitalisation (1·61 [1·44-1·79]) and death (1·61 [1·18-2·21]). Specifically, COVID-19 hospitalisation risk was increased in individuals older than 70 years, and non-COVID-19 hospitalisation risk increased in individuals older than 40 years and death risk in age groups of 50-59 years and 70-79 years. Based on homogeneity testing, no apparent excess risk of any outcome was observed with clozapine exposure compared with other antipsychotics. INTERPRETATION: During antipsychotic exposure compared with unexposed periods, risk of severe infection outcomes increases. It seems reasonable to initiate infection countermeasures, such as pneumococcal vaccination, in people older than 40 years with schizophrenia spectrum disorders, who commence or are treated with antipsychotics. We do not suggest the avoidance of specific antipsychotics but rather adherence to treatment guidelines and a call for increased vigilance regarding this at-risk group. FUNDING: Mental Health Services of the Capital Region of Denmark.

Serum vaccine antibody concentrations in children exposed to perfluorinated compounds.

CONTEXT: Perfluorinated compounds (PFCs) have emerged as important food contaminants. They cause immune suppression in a rodent model at serum concentrations similar to those occurring in the US population, but adverse health effects of PFC exposure are poorly understood. OBJECTIVE: To determine whether PFC exposure is associated with antibody response to childhood vaccinations. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of a birth cohort from the National Hospital in the Faroe Islands. A total of 656 consecutive singleton births were recruited during 1997-2000, [corrected] and 587 participated in follow-up through 2008. MAIN OUTCOME MEASURES: Serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years. RESULTS: Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Among PFCs in maternal pregnancy serum, PFOS showed the strongest negative correlations with antibody concentrations at age 5 years, for which a 2-fold greater concentration of exposure was associated with a difference of -39% (95% CI, -55% to -17%) in the diphtheria antibody concentration. PFCs in the child's serum at age 5 years showed uniformly negative associations with antibody levels, especially at age 7 years, except that the tetanus antibody level following PFOS exposure was not statistically significant. In a structural equation model, a 2-fold greater concentration of major PFCs in child serum was associated with a difference of -49% (95% CI, -67% to -23%) in the overall antibody concentration. A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with odds ratios between 2.38 (95% CI, 0.89 to 6.35) and 4.20 (95% CI, 1.54 to 11.44) for falling below a clinically protective level of 0.1 IU/mL for tetanus and diphtheria antibodies at age 7 years. CONCLUSION: Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years.