Search

Purpose: To investigate diabetic retinopathy (DR) as a potential marker of cardiovascular disease (CVD) in adults with type 1 diabetes attending the Danish DR-screening programme and non-diabetes adults., Methods: In this registry-based matched case-cohort study, we identified 16 547 adults with type 1 diabetes, who were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each case was age- and sex-matched by five non-diabetes individuals (n = 82 399), and odds ratios (ORs) and hazard ratios (HRs) were estimated for incident and upcoming CVD in multivariable models., Results: Adults with type 1 diabetes (median age 44.5 years, 57.6% male) were more likely to have prevalent CVD (OR 1.29; 95% CI, 1.20-1.38) and to develop CVD within 5 years (HR 1.19; 95% CI, 1.08-1.30) as compared to non-diabetes control. However, adults without DR were less likely to develop CVD (HR 0.84; 95% CI, 0.72-0.97) compared to the reference population. For adults with type 1 diabetes, there was an increasing risk for incident CVD for increasing levels of DR (HR 1.33, 1.95, 1.71 and 2.39 for DR-levels 1-4, respectively). Patients with CVD at the time of the first screening had a higher risk to develop DR during follow-up (HR 1.23; 95% CI, 1.02-1.49)., Conclusion: In a nationwide matched case-cohort study adjusted for potential confounders, DR was identified as an independent marker of prevalent and incident CVD in type 1 diabetes with increasing risk demonstrated for higher levels of DR. Likewise, CVD also independently predicted the risk of incident DR., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objectives: To identify diagnostic opportunities, we investigated healthcare-seeking behaviour among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis., Methods: We conducted a population-based, nationwide matched nested case-control study (Denmark, 2009-2021). As cases, we included all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis). We randomly selected controls from the general population and matched 10:1 on date of birth and sex. Exposures were assignment of diagnostic codes for symptoms, contact to medical specialties, medical wandering, and undergoing diagnostic procedures. We calculated the weekly and 3-month proportions of individuals with exposures and calculated absolute risk differences with corresponding 95% CI., Results: We included 1056 cases with LNB and 10 560 controls. Within 3 months before diagnosis, the most frequent assigned symptoms were pain (difference: 13.0%, 95% CI: 10.9-15.1). Cases with LNB exhibited increased contact with most specialties, particularly general practitioners (difference: 48.7%, 95% CI: 46.0-51.4), neurology (difference: 14.3%, 95% CI: 11.7-16.8), and internal medicine (difference: 11.1%, 95% CI: 8.7-13.5), and medical wandering (difference: 17.1%, 95% CI: 14.3-20.0). Common diagnostic procedures included imaging of the brain (difference: 10.2, 95% CI: 8.3-12.1), the spine (difference: 8.8%, 85% CI: 7.0-10.6), and the abdomen (difference: 7.2%, 95% CI: 5.4-9.1). The increase in healthcare-seeking behaviour was observed ≤12 weeks preceding diagnosis., Discussion: Pain appears to be an ambiguous symptom of LNB, potentially contributing to delays in establishing the correct diagnosis. It would be difficult to identify patients with LNB more effectively as the increased healthcare-seeking behaviour preceding diagnosis is distributed across many medical specialties., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with young onset Alzheimer's disease (YOAD) face long diagnostic delays. Prescription medication use may provide insights into early signs and symptoms, which may help facilitate timely diagnosis., Methods: In a register-based nested case-control study, we examined medication use for everyone diagnosed with YOAD in a Danish memory clinic during 2016-2020 compared to cognitively healthy controls. Prescription medication use were grouped into 13 overall categories (alimentary tract and metabolism, blood and blood forming organs, cardiovascular system, dermatologicals, genitourinary system and sex hormones, systemic hormonal preparations, antiinfectives for systemic use, antineoplastic and immunomodulating agents, musculo-skeletal system, nervous system, antiparasitic products, respiratory system, and sensory organs). Further stratifications were done for predetermined subcategories with a use-prevalence of at least 5% in the study population. Conditional logistic regression produced odds ratios, which given the use of incidence-density matching is interpretable as incidence rate ratios (IRRs). The association between prescription medication use and subsequent YOAD diagnosis was examined in the entire 10-year study period and in three time-intervals., Results: The study included 1745 YOAD cases and 5235 controls. In the main analysis, several overall categories showed significant associations with YOAD in one or more time-intervals, namely blood and blood forming organs and nervous system. Prescription medication use in the nervous system category was increased for YOAD cases compared to controls already 10->5 years prior to diagnosis (IRR 1.17, 95% CI 1.05-1.31), increasing to 1.57 (95% CI 1.39-1.78) in the year preceding diagnosis. This was largely driven by antidepressant and antipsychotic use, and especially prominent for first-time users., Conclusions: In this study, medication use in several categories was associated with YOAD. Onset of treatment-requiring psychiatric symptoms such as depression or psychosis in mid-life may serve as potential early indicators of YOAD., (© 2024. The Author(s).)

Objective: This study explored the association of childhood-onset epilepsy (COE) with educational attainment, adulthood employment, and income., Methods: A population-based cohort of 312 children with COE was identified from Tampere University Hospital, Finland. Population Register Center formed a matched random population sample of 1248 children without COE as a reference cohort. The two cohorts were linked to the Statistics Finland database to obtain information on educational attainment, employment status, and income. Fisher's exact test was used to compare employment and graduation. Independent samples t-test was used for analyzing graduation grades and the Mann-Whitney test was used for analyzing yearly income. Results were stratified by sex and disability., Results: During a follow-up of 25 years, a substantially higher proportion of the patients never entered the workforce, 37 % (109/312) compared with 4 % (44/1248) for the referents without COE (p < 0.001). A two-fold difference was observed for COE patients without other disabilities (7.7 %, 13/169, p = 0.01). No clear difference was found in long-term employment between the COE without disabilities and the referents (67 %, 114/169 versus 74 %, 920/1248, p = 0.087). The patients with COE had worse lower secondary school graduation grade averages (7.36 vs 7.6, p = 0.004) and graduation rates (64 % vs 98 %, p < 0.001), the patients without disabilities had similar results to referents (7.43, p = 0.07, 98 %). Of the patients with COE, 18 % graduated from college compared to 38 % of the referents (p < 0.001). The median income was lower in males and females with COE of all ages compared to the referents. The COE patients without additional mental or physical disabilities had income comparable to the healthy referents. 143 patients (46 %) had additional disabilities., Significance: Patients with COE have lower educational attainment, stable employment, and income. Patients without disabilities also have an increased risk of unemployment, but those capable of entering the workforce have stable careers with earnings comparable to the rest of the population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To inform researchers of central considerations and limitations when applying biochemical laboratory-generated registry data in clinical and public health research., Study Design and Setting: After review of literature on registry-based studies and the utilization of clinical laboratory registry data, relevant paragraphs and their applicability toward the creation of considerations for the use of biochemical registry data in research were evaluated. This led to the creation of an initial ten considerations. These were elaborated, edited, and merged after several read-throughs by all authors and discussed thoroughly under influence by the authors' personal experiences with laboratory databases and research registries in Denmark, leading to the formulation of five central considerations with corresponding items and illustrative examples., Results: We recommend that the following considerations should be addressed in studies relying on biochemical laboratory-generated registry data: why are biochemical laboratory data relevant to examine the hypothesis, and how were the variable(s) utilized in the study? What were the primary indications for specimen collection in the study population of interest? Were there any pre-analytical circumstances that could influence the test results? Are data comparable between producing laboratories and within the single laboratory over time? Is the database representative in terms of completeness of study populations and key variables?, Conclusion: It is crucial to address key errors in laboratory registry data and acknowledge potential limitations., Competing Interests: Declaration of competing interest The authors report no conflicts of interest regarding the study presented in this paper. K.A.D. is now an employee of Novo Nordisk A/S., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Early symptoms in young onset Alzheimer's disease (YOAD) may be misinterpreted, causing delayed diagnosis. This population-based study aimed to map morbidity prior to YOAD diagnosis., Methods: In a register-based incidence density matched nested case-control study, we examined hospital-diagnosed morbidity for people diagnosed with YOAD in Danish memory clinics during 2016-2020 compared to controls in a 10-year period. Conditional logistic regression produced incidence rate ratios (IRRs)., Results: The study included 1745 cases and 5235 controls. YOAD patients had a higher morbidity burden in the year immediately before dementia diagnosis, for certain disorders up to 10 years before. This was especially evident for psychiatric morbidity with the highest increased IRRs throughout the entire period and IRR 1.43 (95% confidence interval 1.14-1.79) in the 5-10-years before dementia diagnosis., Discussion: YOAD patients display a different pattern of morbidity up to 10 years prior to diagnosis. Awareness of specific alterations in morbidity may improve efforts toward a timely diagnosis., Highlights: Retrospective, nested case-control study of young onset Alzheimer's disease (YOAD). YOAD cases had a higher morbidity burden than controls. YOAD cases had a higher psychiatric morbidity burden up to 10 years before diagnosis. Altered morbidity patterns could serve as an early warning sign of YOAD., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Improving oxygenation and ventilation in drowning patients early in the field is critical and may be lifesaving. The critical care interventions performed by physicians in drowning management are poorly described. The aim was to describe patient characteristics and critical care interventions with 30-day mortality as the primary outcome in drowning patients treated by the Danish Air Ambulance., Methods: This retrospective cohort study with 30-day follow-up identified drowning patients treated by the Danish Air Ambulance from January 1, 2016, through December 31, 2021. Drowning patients were identified using a text-search algorithm (Danish Drowning Formula) followed by manual review and validation. Operational and medical data were extracted from the Danish Air Ambulance database. Descriptive analyses were performed comparing non-fatal and fatal drowning incidents with 30-day mortality as the primary outcome., Results: Of 16,841 dispatches resulting in a patient encounter in the six years, the Danish Drowning Formula identified 138 potential drowning patients. After manual validation, 98 drowning patients were included in the analyses, and 82 completed 30-day follow-up. The prehospital and 30-day mortality rates were 33% and 67%, respectively. The National Advisory Committee for Aeronautics severity scores from 4 to 7, indicating a critical emergency, were observed in 90% of the total population. They were significantly higher in the fatal versus non-fatal group (p < 0.01). At least one critical care intervention was performed in 68% of all drowning patients, with endotracheal intubation (60%), use of an automated chest compression device (39%), and intraosseous cannulation (38%) as the most frequently performed interventions. More interventions were generally performed in the fatal group (p = 0.01), including intraosseous cannulation and automated chest compressions., Conclusions: The Danish Air Ambulance rarely treated drowning patients, but those treated were severely ill, with a 30-day mortality rate of 67% and frequently required critical care interventions. The most frequent interventions were endotracheal intubation, automated chest compressions, and intraosseous cannulation., (© 2024. The Author(s).)

Objective: Our aim was to identify changes in healthcare utilization prior to a young-onset Alzheimer's disease diagnosis., Methods: In a retrospective incidence density matched nested case-control study using national health registers, we examined healthcare utilization for those diagnosed with young-onset Alzheimer's disease in Danish memory clinics during 2016-2018 compared with age- and sex-matched controls. Negative binomial regression analysis produced contact rate ratios., Results: The study included 1082 young-onset Alzheimer's disease patients and 3246 controls. In the year preceding diagnosis, we found increased contact rate ratios for all types of contacts except physiotherapy. Contact rate ratios for contacts with a general practitioner were significantly increased also > 1-5 and > 5-10 years before diagnosis. The highest contact rate ratios were for psychiatric emergency contacts (8.69, 95% CI 4.29-17.62) ≤ 1 year before diagnosis., Interpretation: Results demonstrate that young-onset Alzheimer's disease patients have increased healthcare utilization from 5 to 10 years prior to diagnosis. Awareness of specific alterations in health-seeking behaviour may help healthcare professionals provide timely diagnoses., (© 2023. The Author(s).)

Background: Identification of socially vulnerable cancer patients in the health care system is difficult. Only little is known concerning changes in the patients' social circumstances during the trajectory. Such knowledge is valuable regarding the identification of socially vulnerable patients in the health care system. The objective of this study was to use administrative data to identify population-based characteristics of socially vulnerable cancer patients and investigate how social vulnerability changed during the cancer trajectory., Methodology: A registry-based social vulnerability index (rSVI) was applied to each cancer patient prior to their diagnosis, and used to assess changes in social vulnerability after the diagnosis., Results: A total of 32,497 cancer patients were included. Short-term survivors (n = 13,994) died from cancer from one to three years after the diagnosis, and long-term survivors (n = 18,555) survived at least three years after the diagnosis. 2452 (18 %) short-term survivors and 2563 (14 %) long-term survivors were categorized as socially vulnerable at diagnosis, of these 22 % and 33 % changed category to not socially vulnerable during the first two years after the diagnosis, respectively. For patients changing status of social vulnerability, several social and health-related indicators changed, which is in line with the complexity of the multifactorial social vulnerability. Less than 6 % of the patients categorized as not vulnerable at diagnosis, changed to become vulnerable during the following two years., Conclusion: During the cancer trajectory, social vulnerability may change in both directions. Surprisingly, more patients, who were categorized as socially vulnerable when their cancer was diagnosed, changed status to not socially vulnerable during follow-up. Future research should attempt to increase knowledge on identifying cancer patients, who experience deterioration after the diagnosis., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: There is a well-known association between mental and behavioral disorders (MBD) and temporomandibular disorder (TMD), although the association has not been established in population-based samples. This study aimed to investigate this relationship using national population-based registry data., Patients and Methods: This case-control study used prospectively collected data from Swedish national registries to investigate exposure to MBD and the probability of developing TMD in all Swedish citizens with hospital-diagnosed or surgically treated TMD between 1998 and 2016. Odds ratios were calculated using conditional logistic regression adjusted for educational level, living area, country of birth, musculoskeletal comorbidity, and history of orofacial/neck trauma., Results: A statistically significant association between MBD and TMD was found for mood affective disorders (OR 1.4), neurotic, stress-related and somatoform disorders (OR 1.7), behavioral syndromes associated with psychological disturbances and physical factors (OR 1.4), disorders of adult personality and behavior (OR 1.4), disorders of psychological development (OR 1.3), behavioral and emotional disorders with onset usually occurring in childhood and adolescence (OR 1.4), and unspecified mental disorder (OR 1.3). The association was stronger for TMD requiring surgery, with the strongest association in patients with disorders of psychological development (OR 2.9). No significant association was found with schizophrenia, schizotypal and delusional disorders, or mental retardation., Conclusion: The findings indicate an increased probability of TMD among patients with a history of certain MBD diagnoses, and a stronger association with TMD requiring surgery, specifically repeated surgery. This highlights the need for improved preoperative understanding of the impact of MBD on TMD, as TMD and chronic pain itself may have a negative impact on mental health., Competing Interests: The authors report no conflicts of interest in this work. All authors approved the final version of this article., (© 2022 Salinas Fredricson et al.)

Rare-disease registries can be useful for studying the associations between environmental exposures and disease severity, but often require the addition of a healthy comparison control group. Defining a surrogate control group, matched and balanced on potentially confounding variables, would allow for the comparison of exposure distributions with cases from a registry. In the present study, we assess whether controls selected externally, using stratification score (SS) matching, can serve as effective proxies for internal controls. In addition, we use methyl paraben (MEPB) to compare the estimated associations between an externally matched sample and case-control frequencies in a cohort with internally matched controls. We started with 225 eligible cases of autism spectrum disorder (ASD) from Childhood Autism Risks from Genetics and the Environment (CHARGE), 241 internal controls from CHARGE, and 265 external controls from the National Health and Nutrition Examination Survey (NHANES) cycles 2005-2016. We calculated the SSs using demographic covariates and matched 1:1 using a caliper method without a replacement. The distribution of the covariates and the mean squared error of the paired differences (MSE paired ) in the SSs between the internal and external group were similar (MSE paired = 0.007 and 0.011, respectively). The association between MEPB and ASD compared to the controls was similar between the externally matched SS pairs and the original frequency matched cohort. Controls selected externally, via SS matching, can provide a comparable bias reduction to that provided by the internal controls, and therefore may be a useful strategy in situations when the internal controls are not available.

Introduction: We aimed to investigate readmission risks following infections in dementia, identify the types of infections behind the risks, and highlight the reasons for readmissions., Methods: Acute inpatient hospital admissions for infections in Danish residents were included from 1 January 2000, or age 65 years. Primary outcomes were 7-day readmissions risk ratios (RRs; risk following infection index admissions of people with dementia relative to those without dementia), risks by infection site, and reasons for readmission. Secondary outcomes were 30- and 90-day readmission risks. Competing risk of death was estimated., Results: Seven-day readmission RR was increased in all age groups and was highest in the youngest patients (women RR: 1.37, 95% confidence interval [CI] 1.22-1.53; men RR: 1.23, 95% CI 1.12-1.35). RRs decreased with increasing age and longer follow-up. The most notable common readmissions were for infections and dehydration in dementia., Conclusions: We conclude that there is a substantially increased readmission risk in people with dementia than in those without dementia, particularly within 7 days, and for the youngest in the cohort. Readmission risks were higher for infection index admissions than for admissions for causes other than infection, and readmissions were mostly due to infections. Our findings highlight the burden of infections in people with dementia and call for in-depth investigations of determinants related to readmission risks, to inform public policy and identify avenues for interventions that can decrease or prevent potentially avoidable readmissions., (© 2021 European Academy of Neurology.)

Maternal thyroid disease, especially hypothyroidism, affects pregnancy and its outcome. In-utero exposure to autoimmune thyroid disease has been reported to associate with childhood ALL in the offspring. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. All patients with their first cancer diagnosis below the age of 20 years were identified from the Finnish Cancer Registry ( n = 2037) and matched for sex and birth year at a 1:5 ratio to population controls identified from the Medical Birth Registry ( n = 10,185). We collected national information on maternal thyroid disease from the Medical Birth Registry, Care Register for Health Care, Register for Reimbursed Drug Purchases and Register of Special Reimbursements. We used conditional logistic regression to analyze childhood cancer risk in the offspring. The adjusted OR for any childhood cancer was 1.41 (95%, CI 1.00-2.00) comparing the offspring of mothers with hypothyroidism and those with normal thyroid function. The risk of lymphomas was increased (adjusted OR for maternal hypothyroidism 3.66, 95%, CI 1.29-10.38). The results remained stable when mothers with cancer history were excluded from the analyses. Maternal hypothyroidism appears to be associated with an increased risk for childhood lymphoma in the offspring. The association exists even after excluding possible familial cancers.

Purpose: Cutaneous melanoma is among the fastest growing malignancies in Norway and ultraviolet radiation (UVR) exposure is the primary environmental risk factor. Immunomodulating drugs can increase skin photosensitivity and suppress immune responses, and by such mechanisms influence melanoma risk. We, therefore, aimed to examine the associations between use of immunomodulating drugs and melanoma risk, at a nationwide population level., Patients and Methods: In the Cancer Registry of Norway, we identified all cases aged 18-85 with a first primary cutaneous melanoma diagnosed in 2007-2015 (n=12,106). These were matched to population controls from the Norwegian National Registry 1:10 (n=118,564), on sex and year of birth using risk set sampling. Information on prescribed drugs (2004-2015) was obtained by linkage to the Norwegian Prescription Database (NorPD). Conditional logistic regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for associations between use of immunomodulating drugs (immunosuppressants and corticosteroids) and melanoma risk, adjusted for ambient UVR and other drug use., Results: Compared with ≤1 prescription, use of ≥8 prescriptions of immunosuppressants was associated with increased risk of melanoma (RR 1.50, 95% CI 1.27, 1.77). Similar associations were found for subgroups of immunosuppressants: drugs typically prescribed to organ transplant recipients (OTRs) (RR 2.02, 95% CI 1.35, 3.03) and methotrexate (RR 1.27, 95% CI 1.04, 1.55). Similar results were found for high levels of cumulative doses and across all histological subtypes. Use of corticosteroids was not associated with melanoma risk., Conclusion: We found a positive association between use of immunosuppressants and melanoma risk, with the highest risk seen for drugs prescribed to OTRs. Knowledge about this risk increase is important for physicians and users of these drugs, for intensified surveillance, awareness and cautious sun exposure., Competing Interests: Øystein Karlstad participates in two Post-Authorization Safety Studies (PASS) unrelated to the submitted work. The studies are on an antidiabetic drug and an anti-psoriasis drug and have been imposed by the European Medicines Agency (EMA). The studies are funded by the marketing authorization holders (Novo Nordisk and Leo Pharma) and are conducted according to the EnCePP Code of Conduct for scientific independence and transparency. The authors report no other potential conflicts of interest related to this work., (© 2020 Berge et al.)

Estimating the prevalence rates of mental disorders is important for developing prevention, treatment, and research plans. Given that survey-based and registry-based prevalence rates of mental disorders each have pros and cons yet complement one another, it is important to consider both assessments when investigating the prevalence rates of mental disorders. However, no study has utilized actual treatment data of patients with mental disorders when investigating the treatment gap. The results of the Survey of Mental Disorders in Korea from 2006, 2011, and 2016 and data from the National Health Insurance Database were used to compare survey-based and registry-based prevalence rates for 17 disorders, as well the prevalence rates for each sex. The survey-based prevalence rate was higher for 10 years in Korea. However, the registry-based prevalence rate continuously increased. By 2016 the two rates were comparable. For alcohol use and nicotine use disorders, the survey-based prevalence rate was consistently higher than the registry-based prevalence rate, while the registry-based prevalence rate was higher for schizophrenia. Mood disorder rates were similar between the two types. Most anxiety disorders had a higher survey-based prevalence rate, except for panic disorder. Men had a higher survey-based prevalence rate, whereas women had a higher registry-based prevalence rate of mental disorders. Korea's registry-based prevalence rate of mental disorders has consistently increased due to various efforts in the field. However, there is still room for improvement, especially in mental health literacy. Therefore, each disorder and patient sex needs to be considered separately when planning education and campaigns., (Copyright © 2020. Published by Elsevier Ltd.)

An association between hematological cancers and inflammatory bowel disease (IBD) has previously been suggested, but the risk of IBD in patients with myeloproliferative neoplasms (MPNs) is unknown. We conducted a nationwide population-based cohort study using Danish registries, to estimate the risk of IBD in individuals diagnosed with essential thrombocythemia, polycythemia vera, myelofibrosis or unclassifiable MPN during 1994-2013. MPN patients were matched 1:10 with sex- and age-matched comparisons. Everyone was followed until a diagnosis of IBD, death/emigration, or 31 December 2013. The risk of IBD overall and according to MPN subtype was calculated using Cox regression and presented as hazard ratios (HRs) with 95% confidence intervals (CI). Of 8207 MPN patients followed for 45,232 person-years, 80 were diagnosed with IBD (61 ulcerative colitis, 19 Crohn's disease). The rate of IBD per 1000 person-years was 1.8 (95% CI:1.4-2.2) in patients vs. 0.8 (95% CI:0.7-0.8) in comparisons, and the absolute 10-year risk of IBD was 0.8% (95% CI:0.6-1.0) in patients vs. 0.4% (95% CI:0.4-0.5) in comparisons. The HR of IBD was 2.4 (95% CI:2.1-2.9) with similar HRs for ulcerative colitis and Crohn's disease. MPN subtype risks varied from 2.1 (95% CI:1.6-2.7) to 2.8 (95% CI:2.1-3.7). Our unselected cohort study showed a more than 2-fold increased risk of IBD in MPN patients.

In this registry-based cohort study, we estimated the risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer in renal transplant recipients (RTRs) compared to a nontransplanted comparison cohort. We identified all first-time RTRs in Denmark during 1990-2015 in a nationwide nephrology register. For each RTR, we randomly selected 50 age- and sex-matched non-RTRs from the background population. The study population was followed for diagnoses of cervical, vaginal, vulvar, penile and anal intraepithelial neoplasia grades 2-3 (IN2/3) and cancer for up to 27 years. We estimated hazard ratios (HRs) of anogenital IN2/3 and cancer in RTRs vs. non-RTRs by Cox regression separately for men and women using age as underlying timescale, adjusting for income, education, HPV vaccination and immunocompromising conditions. We included 4,261 RTRs and 213,673 non-RTRs. RTRs had increased hazard of cervical (HR = 2.1, 95% CI: 1.7-2.8), vaginal (HR = 35.0, 95% CI: 13.9-87.7), vulvar (HR = 16.4, 95% CI: 10.4-25.8), penile (HR = 21.9, 95% CI: 11.1-43.5) and anal (women: HR = 51.1, 95% CI: 28.0-93.1; men: HR = 39.0, 95% CI: 16.7-91.1) IN2/3. The HRs of anogenital cancers were also increased at most sites. The HR of anogenital IN2/3 in female RTRs tended to be higher during graft function than during dialysis. In female RTRs aged <40 years at transplantation, 10-15% had cervical IN2/3 and 5-12% had vaginal/vulvar/anal IN2/3 within 20 years after transplantation, compared to 4-8 and 0.2-0.4%, respectively, of female non-RTRs. In conclusion, RTRs had substantially higher risk of HPV-related anogenital premalignancies and cancer than non-RTRs., (© 2019 UICC.)

Purpose: Melanoma is the cancer with the most rapidly rising incidence rate in Norway. Although exposure to ultraviolet radiation (UVR) is the major environmental risk factor, other factors may also contribute. Antidepressants have cancer inhibiting and promoting side effects, and their prescription rates have increased in parallel with melanoma incidence. Thus, we aimed to prospectively examine the association between use of antidepressants and melanoma by using nation-wide data from the Cancer Registry of Norway, the National Registry, the Norwegian Prescription Database and the Medical Birth Registry of Norway., Patient and Methods: All cases aged 18-85 with a primary cutaneous invasive melanoma diagnosed during 2007-2015 (n=12,099) were matched to population controls 1:10 (n=118,467) by sex and year of birth using risk-set sampling. We obtained information on prescribed antidepressants and other potentially confounding drug use (2004-2015). Conditional logistic regression was used to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs) for the association between overall and class-specific use of antidepressants and incident melanoma., Results: Compared with ≤1 prescription, ≥8 prescriptions of antidepressants overall were negatively associated with melanoma (RR 0.81 CI 0.75-0.87). Class-specific analyses showed decreased RRs for selective serotonin reuptake inhibitors (RR 0.82 CI 0.73-0.93) and mixed antidepressants (RR 0.77 CI 0.69-0.86). The negative association was found for both sexes, age ≥50 years, residential regions with medium and highest ambient UVR exposure, all histological subtypes, trunk, upper and lower limb sites and local disease., Conclusion: Use of antidepressants was associated with decreased risk of melanoma. There are at least two possible explanations for our results; cancer-inhibiting actions induced by the drug and less UVR exposure among the most frequent users of antidepressants., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Berge et al.)

Aims/hypothesis: The workplace is a potentially important arena for prevention of type 2 diabetes and the first step is to identify occupations where the disease is common and/or risk is high. Therefore, our aim was to analyse incidence and prevalence of type 2 diabetes across all occupational groups in Sweden., Methods: This nationwide study included all Swedish citizens born between 1937 and 1979 and gainfully employed between 2001 and 2013 (N = 4,550,892), and followed for a diagnosis of diabetes from 2006 to 2015 (n = 201,717) through national registers. Prevalence in 2013 (mean age 51 years; range 35-67) and age-standardised incidence (per 1000 person-years) were analysed across the 30 most common occupations among men and women. Information on BMI, physical fitness and smoking was obtained through the National Conscription (mean age 18) and Medical Birth Registers (mean age 29)., Results: Prevalence of type 2 diabetes was 5.2% in men and 3.2% in women; in men it was highest among motor vehicle drivers (8.8%) and in women it was highest among manufacturing workers (6.4%). Incidence varied dramatically across occupational groups. In men, it was highest among manufacturing workers (9.41) and professional drivers (9.32) and lowest among university teachers (3.44). In women, incidence was highest in manufacturing workers (7.20) and cleaners (6.18) and lowest in physiotherapists (2.20). We found major differences in the prevalence of being overweight and smoking and in the level of physical fitness across these occupational groups even at young ages., Conclusions/interpretation: Professional drivers, manufacturing workers and cleaners have a threefold increased risk of type 2 diabetes compared with university teachers and physiotherapists. These differences most likely reflect dramatic differences in the prevalence of lifestyle risk factors. If workplace interventions could reduce weight and increase physical activity among employees in these occupations, major health gains may be made.

Hemodialysis is a life-sustaining treatment for persons with kidney failure. However, those on hemodialysis still face a poor quality of life and a short life expectancy. High-quality research evidence from large randomized controlled trials is needed to identify interventions that improve the experiences, outcomes, and health care of persons receiving hemodialysis. With the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, the Innovative Clinical Trials in Hemodialysis Centers initiative brought together Canadian and international kidney researchers, patients, health care providers, and health administrators to participate in a workshop held in Toronto, Canada, on June 2 and 3, 2018. The workshop served to increase knowledge and awareness about the conduct of innovative, pragmatic, cluster-randomized registry trials embedded into routine hemodialysis care and provided an opportunity to discuss and build support for new trial ideas. The workshop content included structured presentations, facilitated group discussions, and expert panel feedback. Partnerships and promising trial ideas borne out of the workshop will continue to be developed to support the implementation of future large-scale trials., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Purpose: Studies show a high level of mental health problems among refugee children. This study examined whether a subset of refugee children living in Denmark accessed psychiatric healthcare services more than those born in the country., Methods: This study compared 24,427 refugee children from Asia, The Middle East, Sub-Saharan Africa and former Yugoslavia, who obtained residency in Denmark between 1 January 1993 and 31 December 2010 with 146,562 Danish-born children, matched 1:6 on age and sex. The study looked at contacts with psychiatric hospitals as well as psychologists and psychiatrists in private practice., Results: Between 1 January 1996 and 30 June 2012, 3.5 % of the refugee children accessed psychiatric healthcare services compared to 7.7 % of the Danish-born children. The rate ratio of having any first-time psychiatric contact was 0.42 (95 % CI 0.40-0.45) among refugee boys and 0.35 (95 % CI 0.33-0.37) among refugee girls, compared to Danish-born children. Figures were similar for those accessing private psychologists or psychiatrists, emergency room, inpatient and outpatient services., Conclusions: Refugee children used fewer psychiatric healthcare services than Danish-born children. This may indicate that refugee children experience barriers in accessing psychiatric healthcare systems and do not receive adequate assessment of their mental health and subsequent referral to specialist services.

Hysterectomy on benign indications is associated with an increased risk for adverse health effects. However, little is known about the association between hysterectomy and subsequent cancer occurrence later in life. The purpose of this study was to assess the effect of hysterectomy on the incidence of cancer. In this population-based cohort study, we used data on 111,595 hysterectomized and 537,9843 nonhysterectomized women from nationwide Swedish Health Care registers including the Inpatient Register, the Cancer Register and the Cause of Death Register between 1973 and 2009. Hysterectomy with or without concomitant bilateral salpingo-ophorectomy (BSO) performed on benign indications was considered as exposure and incidence of primary cancers was used as outcome measure. Rare primary cancers (<100 cases for the two groups combined) were excluded from analysis. A marginal risk reduction for any cancer was observed for women with previous hysterectomy and for those with hysterectomy and concurrent BSO (HR 0.93, 95% CI 0.91-0.95 and HR 0.92, 95% CI 0.87-0.96, respectively). Compared to nonhysterectomized women, significant risks were observed for thyroid cancer (HR 1.76, 95% CI 1.45-2.14). For both hysterectomy and hysterectomy with BSO, an association with brain cancer was observed (HR 1.48, 95% CI 1.32-1.65 and HR 1.45, 95% CI 1.15-1.83, respectively). Hysterectomy, with or without BSO, was not associated with breast, lung or gastrointestinal cancer. We conclude that hysterectomy on benign indications is associated with an increased risk for thyroid and brain cancer later in life. Further research efforts are needed to identify patient groups at risk of malignancy following hysterectomy., (© 2016 UICC.)

In Denmark, the need for monitoring of clinical quality and patient safety with feedback to the clinical, administrative and political systems has resulted in the establishment of a network of more than 60 publicly financed nationwide clinical quality databases. Although primarily devoted to monitoring and improving quality of care, the potential of these databases as data sources in clinical research is increasingly being recognized. In this review, we describe these databases focusing on their use as data sources for clinical research, including their strengths and weaknesses as well as future concerns and opportunities. The research potential of the clinical quality databases is substantial but has so far only been explored to a limited extent. Efforts related to technical, legal and financial challenges are needed in order to take full advantage of this potential., (© 2016 The Association for the Publication of the Journal of Internal Medicine.)

Reproductive factors have been shown to influence cancer risk. Several pathological conditions during pregnancy have also been associated with subsequent altered cancer risk in the mother. Hyperemesis gravidarum (hyperemesis) is an early pregnancy condition characterized by severe nausea and vomiting resulting in weight loss and metabolic disturbances. Studies have reported associations between hyperemesis and cancer, but results are inconsistent. In this nested case-control study we linked the population-based medical birth registries and cancer registries in Norway, Sweden and Denmark in order to examine overall cancer risk and risk of specific cancer types in women with a history of hyperemesis, using conditional logistic regression. In total, 168,501 cases of cancer in addition to up to 10 cancer-free controls per case were randomly sampled, matched on year of birth and birth registry (n = 1,721,626). Hyperemesis was defined through the International Classification of Diseases. Analyses were adjusted for potential confounders. Hyperemesis was inversely associated with overall cancer risk with adjusted relative risk (aRR) of 0.93 (95% CI: 0.88-0.99), with cancer in the lungs (aRR: 0.60, 95% CI: 0.44-0.81), cervix (aRR: 0.66, 95% CI: 0.49-0.91) and rectum (aRR: 0.48, 95% CI: 0.29-0.78). Thyroid cancer was positively associated with hyperemesis (aRR 1.45, 95% CI: 1.06-1.99) and risk increased with more than one hyperemetic pregnancy (aRR 1.80, 95% CI: 1.23-2.63). Hormonal factors, in particular human chorionic gonadotropin, are likely to be involved in mediating these effects. This study is the first to systematically address these associations and provides valuable knowledge on potential long-term consequences of hyperemesis., (© 2015 UICC.)