Cumulative incidence of second primary cancers in a large nationwide cohort of Danish cancer survivors: a population-based retrospective cohort study.

BACKGROUND: A new primary cancer is a serious late effect of a pre-existing cancer diagnosis, and can be attributed to hereditary cancer syndromes, immune or hormonal factors, cancer treatment, or modifiable lifestyle or environmental factors. We investigated the absolute and relative incidence of second primary cancers in a large cohort of Danish cancer survivors. Furthermore, we examined the association between alcohol-related, smoking-related, virus-related, and hormone-related first and second primary cancers. METHODS: In this retrospective cohort study, we identified a cohort of Danish adults (aged ≥40 years) diagnosed with cancer from Jan 1, 1997, to Dec 31, 2014 and alive 1 year after diagnosis. Follow-up was from date of first cancer diagnosis and lasted up to 24 years, ending on Dec 31, 2020. Cohort identification and information on second primary cancers was obtained from the Danish Cancer Registry, and comorbidity and sociodemographic information was obtained from Danish population-based registries. Overall, and for 27 cancer types, cumulative incidence functions and Cox proportional hazard regression models were used to estimate the incidence of second primary cancer and death, and hazard ratios (HRs) and 95% CIs of second primary cancer adjusted for sex, age and year of diagnosis, cohabitation status, income, and comorbidity. FINDINGS: 457 334 Danish adults were included in our study (230 150 [50·3%] male individuals and 227 184 [49·7%] female individuals; median age at diagnosis 68·3 years, IQR 59·7-76·6; median follow-up 3·6 years, IQR 0·6-9·3). The cumulative incidence of second primary cancer increased over time from 6·3% (95% CI 6·2-6·4) 5 years after diagnosis to 10·5% (10·4-10·6) 10 years after diagnosis and to 13·5% (13·4-13·7) 15 years after diagnosis. The highest cumulative incidence of second primary cancer 10 years after diagnosis was observed in survivors of cancers in the larynx (21·8%, 20·5-23·1), oropharynx and oral cavity (19·5%, 18·7-20·3), and bladder and urinary tract (18·5%, 18·0-19·0). Survivors of cancers related to alcohol (HR 1·09, 95% CI 1·06-1·13), smoking (1·73, 1·68-1·78), diet high in red or processed meat (1·32, 1·24-1·39), or virus (1·23, 1·13-1·35) were at increased risk of developing a second cancer with the same aetiology, whereas having had a hormone-related first cancer was associated with lower risk of a second hormone-related cancer (0·77, 0·73-0·81). INTERPRETATION: Our results could help optimise prevention efforts targeting modifiable risk factors to reduce risk of developing a second primary cancer. FUNDING: Nordic Cancer Union and The Health Foundation (Helsefonden).

Impact of multimorbidity and polypharmacy on mortality after cancer: a nationwide registry-based cohort study in Denmark 2005-2017.

BACKGROUND: Concurrent chronic diseases and treatment hereof in patients with cancer may increase mortality. In this population-based study we examined the individual and combined impact of multimorbidity and polypharmacy on mortality, across 20 cancers and with 13-years follow-up in Denmark. MATERIALS AND METHODS: This nationwide study included all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015, and followed until the end of 2017. We defined multimorbidity as having one or more of 20 chronic conditions in addition to cancer, registered in the five years preceding diagnosis, and polypharmacy as five or more redeemed medications 2-12 months prior to cancer diagnosis. Cox regression analyses were used to estimate the effects of multimorbidity and polypharmacy, as well as the combined effect on mortality. RESULTS: A total of 261,745 cancer patients were included. We found that patients diagnosed with breast, prostate, colon, rectal, oropharynx, bladder, uterine and cervical cancer, malignant melanoma, Non-Hodgkin lymphoma, and leukemia had higher mortality when the cancer diagnosis was accompanied by multimorbidity and polypharmacy, while in patients with cancer of the lung, esophagus, stomach, liver, pancreas, kidney, ovarian and brain & central nervous system, these factors had less impact on mortality. CONCLUSION: We found that multimorbidity and polypharmacy was associated with higher mortality in patients diagnosed with cancer types that typically have a favorable prognosis compared with patients without multimorbidity and polypharmacy. Multimorbidity and polypharmacy had less impact on mortality in cancers that typically have a poor prognosis.

Effects of home-based specialized palliative care and dyadic psychological intervention on caregiver burden: results from a randomized controlled trial.

Background The Domus study, a randomized controlled trial (RCT), evaluated the effect of home-based specialized palliative care (SPC) reinforced with a psychological intervention for the patient-caregiver dyad on increasing advanced cancer patients' time spent at home, as opposed to hospitalized, and the number of home deaths. As palliative care extends to include support for patients' families and may thus assist caregivers and decrease demands on them, in this study we evaluated a secondary outcome, caregiver burden.Material and Methods Patients with incurable cancer and their caregivers were randomized (1:1) to care as usual or home-based SPC. Caregiver burden was assessed using the Zarit Burden Interview (ZBI) at baseline and 2, 4, 8 weeks and 6 months after randomization. Intervention effects were assessed in mixed effects models.Results A total of 258 caregivers were enrolled. Eleven per cent of informal caregivers experienced severe caregiver burden at baseline. Caregiver burden increased significantly over time in both groups (p = 0.0003), but no significant effect of the intervention was seen on overall caregiver burden (p = 0.5046) or burden subscales measuring role and personal strain.Conclusion In line with the majority of previous RCTs, the Domus intervention was not able to significantly reduce caregiver burden. Future interventions should consider targeting only caregivers reporting the greatest caregiver burden.

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.

Postoperative epilepsy and survival in glioma patients: a nationwide population-based cohort study from 2009 to 2018.

PURPOSE: Postoperative epilepsy is common in glioma patients and has been suggested to indicate disease progression, yet knowledge of its role as a prognostic factor is limited. This study investigates the association between postoperative epilepsy and survival amongst patients with gliomas. METHODS: We included 3763 patients with histopathologically diagnosed grade II, III, and IV gliomas from 2009 to 2018 according to the Danish Neuro-Oncology Registry. Information on epilepsy diagnosis was redeemed from the Danish National Patient Registry, the National Prescription Registry and the Danish Neuro-Oncology Registry. We used Cox proportional hazards models with 95% confidence intervals (CIs) to examine hazard ratios (HRs) for the association between postoperative epilepsy and risk of death. We examined the role of the timing of epilepsy in three different samples: Firstly, in all glioma patients with postoperative epilepsy; secondly, in patients with postoperative de novo epilepsy; thirdly, exclusively in a homogeneous sub-group of grade IV patients with postoperative de novo epilepsy. RESULTS: Glioma patients with postoperative epilepsy had an increased risk of death, regardless of prior epilepsy status (HR = 4.03; CI 2.69-6.03). A similar increase in the risk of death was also seen in patients with postoperative de novo epilepsy (HR = 2.08; CI 1.26-3.44) and in the sub-group of grade IV patients with postoperative de novo epilepsy (HR = 1.83; CI 1.05-3.21). CONCLUSIONS: Postoperative epilepsy may negatively impact survival after glioma diagnosis, regardless of preoperative epilepsy status. Postoperative epilepsy may be an expression of a more invasive growth pattern of the gliomas following primary tumor treatment.

Risk of somatic hospitalization in parents after cancer in a child, a nationwide cohort study.

OBJECTIVE: The diagnosis of cancer in a child is a profoundly stressful experience. The impact on parents' somatic health, including lifestyle-related diseases, however, is unresolved. This paper assesses parents' risk of hospitalization with somatic disease after a child's cancer diagnosis. METHODS: We conducted a nationwide population- and register-based study with parents of all children under age 20 diagnosed with cancer in Denmark between 1998 and 2013 and parents of cancer-free children, matched (1:10) on child's age and family type. We estimated HR with 95% CI in Cox proportional hazard models for 13 major International Classification of Diseases-10 disease groups, selected stress- and lifestyle-related disease-groups, and investigated moderation by time since diagnosis, parental sex, and cancer type. RESULTS: Among n = 7797 parents of children with cancer compared with n = 74,388 parents of cancer-free children (51% mothers, mean age 42), we found no overall pattern of increased risk for 13 broad disease groups. We found increases in digestive system diseases (HR 1.06, 95% CI 1.01-1.12), genitourinary system diseases (HR 1.08, 95% CI 1.02-1.14), and neoplasms (HR 1.20, 95% CI 1.13-1.27), the latter attributable mostly to increased rates of tobacco-related cancers and mothers' diet-related cancers. CONCLUSIONS: This is the first attempt to document the impact of childhood cancer on parents' somatic health. With the exception of increased risk for neoplasms, likely due to shared genetic or lifestyle factors, our findings offer the reassuring message, that the burden of caring for a child with cancer does not in general increase parents' risk for somatic diseases.

Temporal changes in the probability of live birth among female survivors of childhood cancer: A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries.

BACKGROUND: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births. METHODS: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades. RESULTS: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97]). CONCLUSIONS: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary. LAY SUMMARY: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child.

Psychiatric disorders in individuals with neurofibromatosis 1 in Denmark: A nationwide register-based cohort study.

The aim of this study was to assess the risks of psychiatric disorders in a large cohort of 905 individuals with NF1 and 7614 population comparisons matched on sex and year of birth. The cohort was linked to the Danish Psychiatric Central Research Register to ascertain information on hospital contacts for psychiatric disorders based on the International Classification of Diseases version 8 and 10. The hazard ratio (HR) for a first psychiatric hospital contact was higher in girls (4.19, 95% confidence interval [CI] 1.81-9.69) and boys with NF1 (5.02, 95% CI 3.27-7.69) <7 years of age than in the population comparisons. Both sexes had increased HRs for developmental disorders, including attention deficit/hyperactivity disorders, autism spectrum disorders, and intellectual disabilities in childhood. Females with NF1 had also increased HRs for unipolar depression, other emotional and behavioral disorders, and severe stress reaction and adjustment disorders in early adulthood. The HRs for psychoses, schizophrenia, bipolar disorders, and substance abuse were similar in individuals with NF1 and the population comparisons. Finally, the cumulative incidence of a first hospital contact due to any psychiatric disorder by age 30 years was 35% (95% CI 29-41) in females and 28% (95% CI 19-37) in males with NF1. Thus, screening for psychiatric disorders may be important for early diagnosis and facilitation of appropriate and effective treatment in individuals with NF1.

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.

Total burden of disease in cancer patients at diagnosis-a Danish nationwide study of multimorbidity and redeemed medication.

BACKGROUND: Multimorbidity is a growing challenge worldwide. In this nationwide study, we investigated the prevalence of multimorbidity and polypharmacy at the time of diagnosis across 20 cancers. METHODS: We conducted a nationwide register-based cohort study of all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015. Multimorbidity was defined as one or more of 20 conditions (131 specific diagnoses) registered in the Danish National Patient Registry < 5 years before the cancer diagnosis. Polypharmacy was defined as five or more medications registered in the Danish National Prescription Registry and redeemed twice 2-12 months before the cancer diagnosis. RESULTS: We included 261,745 patients with a first primary cancer, of whom 55% had at least one comorbid condition at diagnosis and 27% had two or more. The most prevalent conditions at the time of cancer diagnosis were cardiovascular disease, chronic obstructive pulmonary disease, diabetes, stroke and depression/anxiety disorder. Polypharmacy was present in one-third of the cancer patients with antihypertensives, anti-thrombotic agents, anti-hyperlipidaemic agents, analgesics and diuretics as the most prevalent redeemed medications. CONCLUSION: Among patients with a newly established cancer diagnosis, 55% had at least one comorbid condition and 32% were exposed to polypharmacy.

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.

Vitamin D-fortified foods improve wintertime vitamin D status in women of Danish and Pakistani origin living in Denmark: a randomized controlled trial.

PURPOSE: Low vitamin D status is prevalent worldwide. We aim to investigate the effect of vitamin D fortification on serum 25-hydroxyvitamin D (25(OH)D) concentration in women of Danish and Pakistani origin at risk of vitamin D deficiency. METHODS: A 12-week randomized, double-blinded, placebo-controlled intervention trial during winter time, designed to provide 20 µg vitamin D3/day through fortified yoghurt, cheese, eggs and crisp bread, and assess the change in serum 25(OH)D. Participants were 143 women of Danish and Pakistani origin, living in Denmark, randomized into four groups, stratified by ethnicity. RESULTS: Mean (SD) baseline 25(OH)D concentrations among women of Danish and Pakistani origin were 49.6 (18) and 46.9 (22) nmol/L, respectively (P = 0.4). While 9% of Danish women had 25(OH)D < 30 nmol/L, the prevalence among women of Pakistani origin was 24%. Median (IQR) vitamin D intake among Danish and Pakistani women at endpoint was 32.0 (27.0, 34.4) µg/day and 24.2 (19.2, 30.8) µg/day, respectively. Endpoint serum 25(OH)D increased in fortified groups to 77.8 (14) nmol/L among Danish women and 54.7 (18) nmol/L among women of Pakistani origin (P < 0.01). At endpoint, 0% in the Danish-fortified group and 3% in the Pakistani-fortified group had 25(OH)D < 30 nmol/L, compared with 23 % and 34% in their respective control groups. CONCLUSIONS: Vitamin D fortification of four different foods for 12 weeks during winter was effective in increasing serum 25(OH)D and reducing the prevalence of very low vitamin D status among women of Danish and Pakistani origin. CLINICALTRIALS. GOV WITH IDENTIFIER: NCT02631629.

Transcription factor FOXP3: A repressor of the TFPI gene?

Single nucleotide polymorphisms (SNPs) may play an important role in the risk of certain diseases. We have previously shown that the -287T/C SNP of the tissue factor pathway inhibitor (TFPI) gene promoter region exerts differential impact on TFPI mRNA expression; the C allele being associated with higher TFPI expression, which in turn is associated with reduced risk of thrombosis. In the present study, we aimed to reveal the underlying molecular mechanisms using human embryonic kidney 293 (HEK293) and Michigan Cancer Foundation-7 (MCF7) cells that both express TFPI. Transfecting the cells with luciferase reporter gene constructs containing the TFPI promoter with either the T or the C allele of -287T/C resulted in increased luciferase activity with the C allele relative to the T allele. Three potential candidate transcription factors for binding to the two -287 alleles were predicted using the ALGGEN PROMO software, and results from electrophoretic mobility shift assays indicated that forkhead box protein 3 (FOXP3), initially identified as a functional marker of T regulator cells, bound more specifically to the T allele compared with the C allele. By chromatin immunoprecipitation assays analysis it was confirmed that FOXP3 was able to bind to the DNA region that contains the SNP. Knockdown or overexpression of FOXP3 resulted in increased or decreased TFPI levels, respectively, in both cell types. In conclusion, this study indicates that FOXP3 most likely is involved in the increased levels of TFPI observed with the -287C allele and also that FOXP3 might be a repressor for TFPI expression.