Loneliness and the risk of type 2 diabetes.

INTRODUCTION: The incidence of type 2 diabetes is increasing globally. Recent research suggests that loneliness could be a potential risk factor for the development of type 2 diabetes. We aimed to investigate the association between loneliness and type 2 diabetes and the modifying effect of mental disorders. RESEARCH DESIGN AND METHODS: We conducted a prospective study including 465 290 adults (aged ≥16 years) who participated in either the Danish Health and Morbidity Survey or the Danish National Health Survey between 2000 and 2017. Loneliness was based on self-report, while type 2 diabetes was measured using an algorithm combining several health registers including type 2 diabetes patients treated both within the hospital sector and general practice. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During a mean follow-up time of 6.3 years, 13 771 individuals (3%) developed type 2 diabetes. Feeling lonely once in a while was associated with a 14% increased risk of type 2 diabetes (95% CI 1.09 to 1.20), while feeling lonely often was associated with a 24% increased risk (95% CI 1.14 to 1.34), independent of sociodemographic factors and body mass index. The association was stronger among individuals without a mental disorder (HR 1.21, 95% CI 1.10 to 1.34 among those feeling lonely often) compared with those with a mental disorder (HR 1.07, 95% CI 0.93 to 1.23). CONCLUSIONS: Loneliness independently increased the risk of type 2 diabetes. The effect was more pronounced in individuals without a mental disorder, as having a mental disorder itself likely increases the risk of type 2 diabetes. These findings emphasize the importance of addressing loneliness as a modifiable risk factor in preventing type 2 diabetes.

Educational outcomes and the role of comorbidity among adolescents with type 1-diabetes in Denmark.

AIMS: To examine educational outcomes among adolescents with type 1 diabetes and determine the role of comorbidity. METHODS: We conducted a nationwide register-based cohort study including 3370 individuals born between 1991 and 2003 and diagnosed with type 1 diabetes before the age of 16. They were all matched with up to four individuals without type 1 diabetes on age, gender, parents' educational level and immigration status. Information on comorbidity was based on hospital diagnoses. The individuals were followed in registers to determine whether they finished compulsory school (9th grade, usually at the age of 15-16 years), and were enrolled in secondary education by age 18 years. RESULTS: Individuals with type 1 diabetes were more likely not to complete compulsory school (OR 1.44, 95% CI 1.26-1.64), and not being enrolled in an upper secondary education by age 18 (OR 1.50, 95% CI 1.31-1.73) compared to their peers. A total of 1869 (56%) individuals with type 1 diabetes were registered with at least one somatic (n = 1709) or psychiatric comorbidity (n = 389). Those with type 1 diabetes and psychiatric comorbidity were more likely not to complete compulsory school (OR 2.47, 95% CI 1.54-3.96), and not being enrolled in an upper secondary education by age 18 (OR 3.66, 95% CI 2.27-5.91) compared to those with type 1 diabetes only. Further, there was a tendency towards an association between having somatic comorbidity and adverse educational outcomes (OR 1.25, 95% CI 0.97-1.63; OR 1.26, 95% CI 0.95-1.66) among adolescents with type 1 diabetes. The associations differed markedly between diagnostic comorbidity groups. CONCLUSION: Type 1 diabetes affects educational attainment and participation among adolescents. Psychiatric comorbidity contributes to adverse educational outcomes in this group, and there is a tendency that somatic comorbidity also plays a role.

Diabetic complications and risk of depression and anxiety among adults with type 2 diabetes.

AIMS: To investigate if diabetic complications increase the risk of depression and/or anxiety among adults with type 2 diabetes. METHODS: This register-based, prospective study included 265,799 adult individuals diagnosed with type 2 diabetes between 1997 and 2017 without a recent history of depression or anxiety. Diabetic complications included cardiovascular disease, amputation of lower extremities, neuropathy, nephropathy and retinopathy. Both diabetic complications and depression and anxiety were defined by hospital contacts and prescription-based medication. All individuals were followed from the date of type 2 diabetes diagnosis until the date of incident depression or anxiety, emigration, death or 31 December 2018, whichever occurred first. RESULTS: The total risk time was 1,915,390 person-years. The incidence rate of depression and/or anxiety was 3368 per 100,000 person-years among individuals with diabetic complications and 1929 per 100,000 person-years among those without. Having or developing any diabetic complication was associated with an increased risk of depression and/or anxiety (HR 1.77, 95% CI 1.73-1.80). The risk for depression and/or anxiety was increased for all types of diabetic complications. The strongest association was found for amputation of lower extremities (HR 2.16, 95% CI 2.01-2.31) and the weakest for retinopathy (HR 1.13, 95% CI 1.09-1.17). CONCLUSION: Individuals with type 2 diabetes and diabetic complications are at increased risk of depression and anxiety. This points towards the importance of an increased clinical focus on mental well-being among individuals with type 2 diabetes and complications.

The association between education and fear of recurrence among breast cancer patients in follow-up - and the mediating effect of self-efficacy.

BACKGROUND: Major restructuring of surveillance after breast cancer treatment with less follow-up consultations may result in insecurity and fear of recurrence (FCR) among the less resourceful breast cancer patients. We investigate the association between breast cancer patients' education and FCR and if self-efficacy mediates the associations between education and FCR. MATERIAL AND METHODS: A questionnaire survey was conducted from 2017 to 2019, among 1773 breast cancer patients shortly after having their follow-up switched from regular outpatient visits with an oncologist to either nurse-led or patient-initiated follow-up, with a subsequent questionnaire after 12 months. Data on disease and treatment characteristics were extracted from medical records and the Danish Breast Cancer Group Database. Logistic regression analyses were used to examine the association between education and FCR. Separate analyses were conducted for patients ≤ and >5 years since diagnosis and all models were adjusted for age and cohabitation status. To explore potential mediation by self-efficacy, we conducted regression analyses on education and FCR further adjusting for self-efficacy. RESULTS: The participation rate was 57%, and after the exclusion of patients due to missing data, 917 were included in analyses. Patients with long education had significantly less FCR compared to patients with short education (OR (95% CI) 0.71 (0.51;0,99)). When separated by time since diagnosis, there was no association among patients >5 years since diagnosis while the OR was 0.51 (95% CI, 0.30;0.85) for patients ≤5 years since diagnosis. Further adjusting for self-efficacy among patients <5 years since diagnosis resulted in an OR of 0.56 (95% CI, 0.33;0.95) among patients with long compared to short education. CONCLUSION: Up to 5 years after diagnosis, breast cancer patients with long education are less likely to experience FCR than patients with short education. Self-efficacy mediated only a very small part of this association, indicating that other factors play a role in socioeconomic differences in FCR among breast cancer patients.

Mortality patterns in a Danish nationwide cohort of persons with intellectual disabilities.

Mortality disparities among persons with intellectual disability are important to guide health-care practices. The objective was to evaluate mortality patterns of persons with intellectual disability in a nationwide study from 1976 to 2020. This study establishes a Danish nationwide cohort of persons with intellectual disability and age- and sex-matched reference cohort through linkage between several registers. We established a cohort of 79,114 persons with intellectual disability. Standardized mortality ratios were increased for persons with intellectual disability, most pronounced among younger persons and among females. Life expectancies were markedly lower; among persons with intellectual disability 63.6 years among females and 59.8 years among males in 2016-2020 compared to 82.4 and 78.7 years among females and males in the reference cohort. Life expectancies decreased with severity of intellectual disability. This study reports the establishment of a nationwide Danish cohort of persons with intellectual disability.

Breast Cancer Screening Among Women With Intellectual Disability in Denmark.

Importance: Breast cancer-specific mortality is increased among women with intellectual disability (ID), and knowledge about participation in breast cancer screening in this group is needed. Objective: To examine participation in the Danish national breast cancer screening program among women with ID compared with women without ID. Design, Setting, and Participants: This dynamic population-based cohort study assessed participation in the Danish national breast cancer screening program initiated in 2007, targeting women aged 50 to 69 years with a screening interval of 2 years. In all, 6357 women with ID born between 1941 and 1967 and eligible for the screening program were identified in national registers. Women entered the study between January 1, 2007, and December 31, 2017. Subsequently, 273 women were excluded due to a history of carcinoma in situ or breast cancer, and 489 due to registration errors in registers. Each woman was individually age-matched with 10 women without ID (reference group). All women were followed up until March 31, 2021, or censoring (due to death, carcinoma in situ, or breast cancer). Data were analyzed from December 1, 2021, to June 31, 2022. Exposures: Intellectual disability was defined as being registered with an ID diagnosis or a diagnosis most likely leading to ID or residing at an institution for persons with ID. Main Outcomes and Measures: Participation in breast cancer screening (fully, partly, and never). Results: A total of 5595 women with ID and 49 423 age-matched women in the reference group were included in the analysis. Of these, 2747 women with ID (49%) and 24 723 in the reference group (50%) were 50 years of age at study entry; for those older than 50 years, the median age was 51 years (IQR, 50-58 years) in both groups. In all, 1425 women with ID (25%) were fully screened according to guidelines for the Danish breast cancer screening program compared with 30 480 women in the reference group (62%). Women with ID had nearly 5 times higher odds of never being screened compared with the reference group (odds ratio, 4.90 [95% CI, 4.60-5.22]). In all, 2498 women with ID (45%) and 6573 in the reference group (13%) were never screened. The proportion of never-screened women increased with severity of ID, from 834 of 2287 (36%) among women with mild ID to 173 of 212 (82%) among women with profound ID. Conclusions and Relevance: The findings of this cohort study suggest that women with ID are markedly less likely to participate in breast cancer screening compared with women without ID. These findings further suggest a need for tailored guidelines and approaches for breast cancer screening in this group of women.

Socioeconomic inequality in cancer in the Nordic countries. A systematic review.

BACKGROUND: Despite structural and cultural similarities across the Nordic countries, differences in cancer survival remain. With a focus on similarities and differences between the Nordic countries, we investigated the association between socioeconomic position (SEP) and stage at diagnosis, anticancer treatment and cancer survival to describe patterns, explore underlying mechanisms and identify knowledge gaps in the Nordic countries. METHODS: We conducted a systematic review of population based observational studies. A systematic search in PubMed, EMBASE and Medline up till May 2021 was performed, and titles, abstracts and full texts were screened for eligibility by two investigators independently. We extracted estimates of the association between SEP defined as education or income and cancer stage at diagnosis, received anticancer treatment or survival for adult patients with cancer in the Nordic countries. Further, we extracted information on study characteristics, confounding variables, cancer type and results in the available measurements with corresponding confidence intervals (CI) and/or p-values. Results were synthesized in forest plots. RESULTS: From the systematic literature search, we retrieved 3629 studies, which were screened for eligibility, and could include 98 studies for data extraction. Results showed a clear pattern across the Nordic countries of socioeconomic inequality in terms of advanced stage at diagnosis, less favorable treatment and lower cause-specific and overall survival among people with lower SEP, regardless of whether SEP was measured as education or income. CONCLUSION: Despite gaps in the literature, the consistency in results across cancer types, countries and cancer outcomes shows a clear pattern of systematic socioeconomic inequality in cancer stage, treatment and survival in the Nordic countries. Stage and anticancer treatment explain some, but not all of the observed inequality in overall and cause-specific survival. The need for further studies describing this association may therefore be limited, warranting next step research into interventions to reduce inequality in cancer outcomes. STUDY REGISTRATION: Prospero protocol no: CRD42020166296.

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.

Is the health literacy of informal caregivers associated with the psychological outcomes of breast cancer survivors?

PURPOSE: To investigate whether health literacy (HL) among informal caregivers of breast cancer (BC) survivors is associated with patient psychological outcomes. METHODS: We used data (n = 340 pairs) from baseline questionnaires administered in the MyHealth trial investigating nurse-led BC follow-up. All BC survivors and their invited caregivers were included immediately after completion of primary treatment. We performed multivariate regression analyses to examine the association between caregiver HL (nine dimensions as measured by the Health Literacy Questionnaire) as exposure and patient depression, anxiety, and health-related quality of life (HQoL) as outcomes. We further examined whether any association differed according to type of caregiver, patient HL, and patient activation (skill in managing one's health). RESULTS: Three dimensions, "ability to engage with providers" (ß = - 0.2), "navigating the system" (ß = - 0.2), and "understand health information" (ß = - 0.2), were significantly associated with lower patient depression (p < 0.05), while four dimensions, "having sufficient information" (ß = 0.3), "navigating the system" (ß = 0.2), "find health information" (ß = 0.2), and "understand health information" (ß = 0.2), were significantly associated with better patient HQoL (p < 0.05). No significant associations were found for anxiety. Patient HL and activation did not significantly modify the associations, while certain associations for depression were stronger in patients with non-partner caregivers. CONCLUSIONS: The HL of informal caregivers may play an important role in optimizing psychological outcomes in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Involving informal caregivers, who can provide support related to health information and services, may be beneficial for the psychological well-being of cancer survivors.

Registrations of Patients with Renal Cell Carcinoma in the Nationwide Danish Renal Cancer Database versus the Danish Cancer Registry: Data Quality, Completeness and Survival (DaRenCa Study-3).

BACKGROUND: The Danish multidisciplinary renal cancer group (DaRenCa) established the nationwide database DaRenCaData in 2010. The Danish Cancer Registry (DCR) has been considered the golden standard. In contrast to DCR, DaRenCaData required the diagnosis to be histologically or cytologically verified. DaRenCaData and DCR have not previously been compared. PATIENTS AND METHODS: We included patients with renal cell carcinoma registered in DaRenCaData and/or DCR from August 1st 2010 to December 31st 2015. We computed completeness and positive predictive value (PPV) of a diagnosis in DaRenCaData compared with DCR, 1-year, 3-year and 5-year mortality rate ratios, and relative survival. RESULTS: We identified 4890 patients in the two registries. Of these, 4326 were registered in DaRenCaData and 4714 in DCR. Completeness of DaRenCaData was 88% [95% CI, 87-89%] and increased during the period from 82% to 94%. The PPV was 96% [95% CI, 95-97%]. A total of 4150 patients (85%) were found in both registries, 4% (176 patients) in DaRenCaData only, and 12% (564 patients) in DCR only. The relative survival was higher for patients in DaRenCaData vs DCR; the 1-year and 5-year relative survival was 85% vs 81% and 65% vs 59%, respectively. Compared with patients registered in both registries, the mortality rates were higher in patients registered in DaRenCaData only (1-year hazard ratio (HR)=2.84 [95% CI, 2.20-3.68]) or DCR only (1-year HR=4.29 [95% CI, 3.72-4.93]). Observed in both registries, survival improved over time with a 7% yearly reduction in death based on estimations of 1-year mortality rate ratios. CONCLUSION: DaRenCaData had high and increasing completeness and high PPV, establishing it as a high-quality research database. Observed in both registries, renal cell carcinoma mortality declined over time; patients only registered in DCR or DaRenCaData had poorer outcomes. This study points to the importance of assessing the inclusion criteria when interpreting registry-based studies.

Gynaecological cancer leads to long-term sick leave and permanently reduced working ability years after diagnosis.

PURPOSE: The aim of the study was to investigate overall patterns in labour market affiliation, risk for permanently reduced work ability and prevalence of long-term sickness absence among women diagnosed with gynaecological cancer. METHODS: We followed 8451 women diagnosed with ovarian, endometrial or cervical cancer, and 72,311 women with no history of cancer in nationwide registers for up to 19 years (mean 7.5 years). We computed hazards ratios for permanently reduced working ability and annual proportions of long-term sick leave. RESULTS: Patterns of labour market affiliation varied by cancer diagnosis and stage. The hazard of permanently reduced working ability was increased for survivors of all three cancers but most pronounced for women diagnosed with advanced ovarian cancer. The highest hazard ratios were found 2-5 years after diagnosis, and they persisted for years in all groups and throughout the follow-up period of 19 years in women diagnosed with advanced cervical cancer. In the subgroups of women who continued to be potentially active on the labour market, long-term sick leave was more prevalent among cancer survivors than women with no history of cancer up to 10 years after diagnosis. CONCLUSIONS: Women diagnosed with localised as well as advanced gynaecological cancer are at prolonged risk for permanently reduced working ability and long-term sick leave. IMPLICATIONS FOR CANCER SURVIVORS: Gynaecological cancer can have long-term as well as permanent consequences for working ability, and survivors who remain active on the labour market might have to take more sick leave even years after cancer diagnosis than other women at their age.

MyHealth: specialist nurse-led follow-up in breast cancer. A randomized controlled trial - development and feasibility.

Background: Traditionally, women treated for breast cancer (BC) have been followed up through regular oncologist-led visits in outpatient clinics, focusing on detection of recurrences, new primary BC, symptom management, and psychological support. However, this follow-up routine is expensive and its effectiveness has been questioned. Consequently, alternative follow-up programs have been tested. The Guided Self-Determination method (GSD), which facilitates partnership between health-care provider and patient, has been shown to improve self-management in patients with chronic conditions, including cancer. Patient-reported outcomes (PRO) is another increasingly used tool to improve patient-provider communication, symptom monitoring and control. In combination, GSD and PRO may have the potential to meet the objectives of BC follow-up. To test this, we developed the MyHealth study, a randomized controlled trial comparing a nurse-led follow-up program based on GSD, collection of PRO, and patient navigation with routine oncologist-led follow-up. Here we describe how we developed the intervention and are currently testing the feasibility of the MyHealth protocol in terms of recruitment, adherence to the intervention, collection of PRO, and patient navigation. Material and methods: We have invited the first 25 consecutively enrolled patients to test the MyHealth intervention. This consists of (1) 3-5 initial GSD appointments with a nurse, (2) collection of PRO, and (3) symptom management and patient navigation. The randomized trial was launched in January 2017 and is still recruiting. Results of the feasibility study: Of 32 patients invited, 25 accepted participation. At 18-month follow-up, two patients have withdrawn, 143 PRO questionnaires have been completed (mean 5.7/patient) resulting in 59 nurse contacts (mean 2.4 per patient) and 14 project physician contacts (mean 0.6 per patient). Conclusion: A high recruitment rate and response rate to PRO indicate that follow-up led by specialist nurses, based on collection of PRO is feasible and acceptable for patients treated for early stage BC.

Pharmaceutically treated anxiety but not depression prior to cancer diagnosis predicts the onset of cardiovascular disease among breast cancer survivors.

PURPOSE: To examine the associations between pharmaceutically treated anxiety and depression present in the year prior to breast cancer diagnosis and the risk of incident cardiovascular disease (CVD), while controlling for traditional cardiovascular risk factors and clinical characteristics in a population-based observational study. METHODS: Adult 1-year breast cancer survivors (n = 7227), diagnosed between 01-01-1999 and 12-31-2010, with no history of CVD, were selected from the Netherlands Cancer Registry. Drug dispensing data were derived from the PHARMO Database Network and used as proxy for CVD, anxiety, and depression. By multivariable Cox regression analysis, we examined the risk associated with pharmaceutically treated anxiety and depression for developing CVD after cancer diagnosis, adjusting for age, pharmaceutically treated hypertension, hypercholesterolemia, and diabetes mellitus in the year prior to cancer diagnosis, tumor stage, and cancer treatment. RESULTS: During the 13-year follow-up period, 193 (3%) breast cancer survivors developed CVD. Women pharmaceutically treated for anxiety in the year prior to their cancer diagnosis had a 48% increased hazard for CVD [HR = 1.48; 95% CI 1.05-1.08] after full adjustment. This association was restricted to breast cancer survivors who were 65 years or younger. Depression was not associated with CVD risk [HR = 0.89; 95% CI 0.52-1.53]. Older age [HR = 1.06; 95% CI 1.05-1.08], hypertension [HR = 1.80; 95% CI 1.32-2.46], and hypercholesterolemia [HR = 1.63; 95% CI 1.15-2.33] were associated with an increased hazard for incident CVD, whereas hormone therapy [HR = 0.59; 95% CI 0.42-0.83] was protective. CONCLUSIONS: Anxiety present in the year prior to breast cancer diagnosis increases the risk of incident CVD in 1-year breast cancer survivors, after adjustment for depression, traditional cardiovascular risk factors, and clinical characteristics.

Sequence analysis to assess labour market participation following vocational rehabilitation: an observational study among patients sick-listed with low back pain from a randomised clinical trial in Denmark.

INTRODUCTION: The return-to-work (RTW) process after long-term sickness absence is often complex and long and implies multiple shifts between different labour market states for the absentee. Standard methods for examining RTW research typically rely on the analysis of one outcome measure at a time, which will not capture the many possible states and transitions the absentee can go through. The purpose of this study was to explore the potential added value of sequence analysis in supplement to standard regression analysis of a multidisciplinary RTW intervention among patients with low back pain (LBP). METHODS: The study population consisted of 160 patients randomly allocated to either a hospital-based brief or a multidisciplinary intervention. Data on labour market participation following intervention were obtained from a national register and analysed in two ways: as a binary outcome expressed as active or passive relief at a 1-year follow-up and as four different categories for labour market participation. Logistic regression and sequence analysis were performed. RESULTS: The logistic regression analysis showed no difference in labour market participation for patients in the two groups after 1 year. Applying sequence analysis showed differences in subsequent labour market participation after 2 years after baseline in favour of the brief intervention group versus the multidisciplinary intervention group. CONCLUSION: The study indicated that sequence analysis could provide added analytical value as a supplement to traditional regression analysis in prospective studies of RTW among patients with LBP.

Associations between education and physical functioning and pain in adult Danish cancer survivors.

BACKGROUND: Late effects after cancer diagnosis and treatment are common, but only few studies have examined the role of social factors in developing these late effects. The aim of this study was to examine the association between educational level and physical function and pain among cancer survivors two years after diagnosis. MATERIAL AND METHODS: The study population consisted of adult Danish patients with a first-time cancer diagnosis who were sent a questionnaire in 2010 and followed up in 2012. In total, 4346 returned the first questionnaire shortly after diagnosis and 2568 returned the follow-up questionnaire. After exclusion of 177 due to missing information, we included 2391 cancer survivors in the analyses. Physical function and pain were measured using the EORTC QLQ-C30. Linear regression analyses were conducted separately for men and women, and adjusted for demographic and clinical characteristics. Additionally, analyses were stratified on comorbidity. RESULTS: Differences in mean scores according to educational level were small. Physical function was better in women with medium (2.8; 95% CI 0.1;5.4) and higher education (3.4; 95% CI 0.9;5.9) compared to women with short education. In contrast, men with medium education reported lower physical function (-2.9; 95% CI -5.7;-0.1) than men with short education. Compared to women with short education, we found lower pain scores among women with medium (-5.0; 95% CI -8.7;-1.4) and higher education (-3.4; 95% CI -6.7;0.0). Similarly, men with higher education experienced lower pain score (-3.4; 95% CI -6.9;0.1) than men with short education. The role of educational level differed between those with and without comorbidity. CONCLUSION: Educational level is slightly associated with physical function and pain among cancer survivors. However, mean differences in this study were small and below what is considered clinically relevant.