Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients.

INTRODUCTION: Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence. METHODS: We included stage I-III premenopausal breast cancer patients diagnosed during 2002-2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns. RESULTS: We identified three adherence patterns among 4,353 women-high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers. CONCLUSIONS: Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.

Risk of Cancer in Patients With Diverticular Disease: A Population-Based Cohort Study.

BACKGROUND & AIMS: Several studies have investigated the association between diverticular disease (DD) and colorectal cancer. However, whether there is an association between DD and malignancies other than those in the colorectum remains uncertain. METHODS: For the 1978-2019 period, we conducted a nationwide, population-based cohort study using national Danish health care data. We followed patients with DD for up to 20 years, beginning 1 year after the date of DD diagnosis until the first occurrence of incident cancer, emigration, death, 20 years of follow-up, or December 31, 2019. We calculated cumulative incidence proportions of cancer and standardized incidence ratios (SIRs) comparing cancer incidence among patients with DD with that in the general population. RESULTS: We identified 200,639 patients with DD, of whom 20,498 were diagnosed with cancer during the 1-20 years after their DD diagnosis. The SIRs were increased for most cancer sites except for those in the colorectum (SIR, 0.75; 95% confidence interval, 0.72-0.78). The highest SIRs were observed for cancers of the lung, bronchi, and trachea (SIR, 1.20; 95% confidence interval, 1.15-1.24) and kidney (SIR, 1.27; 95% confidence interval, 1.16-1.39). CONCLUSIONS: Our findings show an increased long-term relative risk of cancer following a diagnosis of DD. These findings are likely caused by prevalence of numerous risk factors in patients with DD that confer an increased risk of cancer. The decreased relative risk of colorectal cancer might be explained by an increased likelihood of patients with DD undergoing colonoscopy with polypectomy.

Urticaria and the risk of cancer: a Danish population-based cohort study.

BACKGROUND: Urticaria has been tentatively linked to cancer, but epidemiological evidence supporting this link is sparse and conflicting. We therefore conducted a population-based cohort study using healthcare databases of the Danish population (January 1980-December 2022). We followed 87,507 people for a median of 10.1 years after first hospital contact for urticaria. OBJECTIVES: To examine associations of a hospital diagnosis of urticaria with incident cancer. METHODS: We computed absolute risk of cancer and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) standardized to Danish national cancer rates. In a cross-sectional analysis, we examined whether the extent of cancer spread differed between people with vs. without a previous urticaria diagnosis. RESULTS: The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11) based on 7,788 observed vs. 7,161 expected cases. The risk for any cancer was 0.7% (95% CI, 0.6-0.7) for the first year of follow-up. Cancer was diagnosed in 588 people with urticaria during the first year of follow-up (SIR 1.49, 95% CI, 1.38-1.62) and in 7,200 people thereafter (SIR 1.06, 95% CI, 1.04-1.09). During the first year of follow-up, we found strong associations with hematological cancers (e.g., non-Hodgkin lymphoma SIR 2.91, 95% CI, 1.92-4.23). Cancer stage was similar in people with vs. without previous urticaria diagnosis. CONCLUSIONS: At the time of urticaria diagnosis, or in the first year afterwards, we found a large increase in the risk for cancer. In subsequent years, a persistent 6% increase in risk remained. Diagnostic efforts may partly explain the elevated short-term risk, but occult cancer may promote urticaria, or cancer and urticaria share common risk factors.

Prevalence of Colorectal Neoplasms and Mortality in New Users of Low-Dose Aspirin With Lower Gastrointestinal Bleeding.

BACKGROUND: Aspirin inhibits platelet function and may therefore accelerate early lower gastrointestinal bleeding (LGIB) from colorectal cancer (CRC) precursor polyps. The bleeding may increase endoscopic polyp detection. STUDY QUESTION: To estimate the prevalence of polyps and CRC comparing new users of low-dose aspirin with nonusers who all received a diagnosis of LGIB and to investigate the mortality among these patients. STUDY DESIGN: Using Danish nationwide health registries, we conducted a cohort study (2006-2013) of all new aspirin users who also received a diagnosis of LGIB (n = 40,578). Each new user was matched with 5 nonusers with LGIB by gender and age at the LGIB diagnosis date. MEASURES AND OUTCOMES: We computed the prevalence and prevalence ratios (PRs) of colorectal polyps and CRCs, and the mortality ratios within 6 months after the LGIB, comparing new users with nonusers. RESULTS: We identified 1038 new aspirin users and 5190 nonusers with LGIB. We observed 220 new users and 950 nonusers recorded with endoscopically detected polyps. New aspirin users had a higher prevalence of conventional {PR = 1.28 [95% confidence interval (CI): 1.06-1.55]} and serrated [PR = 1.31 (95% CI: 0.95-1.80)] polyps. New users and nonusers had a similar prevalence of CRC [PR = 1.04 (95% CI: 0.77-1.39)]. However, after stratifying by location of CRC, the prevalence of proximal tumors was lower [PR = 0.71 (95% CI: 0.35-1.43)] in new users than in nonusers. No difference in mortality was observed. CONCLUSIONS: These findings indicate that new use of low-dose aspirin is associated with an increased detection of colorectal polyps compared with nonuse.

Risk factors and lifelong impact of community-acquired pneumonia in congenital heart disease.

INTRODUCTION: The prevalence of congenital heart disease (CHD) in adults is rising necessitating a greater understanding of acquired diseases such as community-acquired pneumonia, which remains a leading cause of age-related mortality and morbidity in the general population. We hypothesise that the CHD population, given cardiopulmonary mechanics and altered immune function, bears a uniquely high risk for pneumonia-related hospitalisations and mortality. METHODS: A countrywide cohort study was performed to calculate the relative risk and cumulative incidence of pneumonia hospitalisations and resultant 30-day mortality amongst the adult CHD population, matched 1:10 with non-CHD persons by gender, age, and adjusted for comorbidities. Cox proportional hazard regression quantified the impact of CHD severity and extracardiac defects. RESULTS: The CHD cohort includes 17,162 adults. The majority demonstrate mild/moderate CHD complexity. The cumulative incidence of pneumonia hospitalisation was higher for adults with CHD (hazard ratio 1.90; 95% confidence interval: 1.74-2.06) than the comparison cohort. This risk was increased for those with extracardiac defects or a syndrome (hazard ratio: 4.34; 95% confidence interval: 3.39-5.54). Additionally, CHD individuals with severe/univentricular subtypes demonstrate a heightened risk compared to the non-CHD cohort (hazard ratio: 2.35; 95% confidence interval: 1.94-2.84), as well as compared to those with mild/moderate CHD (hazard ratio: 1.28; 95% confidence interval: 1.07-1.53). In addition, pneumonia hospitalisation mortality was elevated above the comparison population with a 30-day mortality rate ratio of 1.31 (95% confidence interval: 1.00-1.73). CONCLUSION: Adults with CHD are at elevated risk of pneumonia hospitalisations and pneumonia-associated mortality. This risk is further elevated in those with severe CHD and extracardiac defects.

Risk of cancer in patients with epistaxis and haemoptysis.

This corrects the article DOI: 10.1038/bjc.2017.85.

Risk of venous thromboembolism in patients with mycosis fungoides and parapsoriasis: A Danish nationwide population-based cohort study.

BACKGROUND: Mycosis fungoides (MF) and parapsoriasis are characterized by malignant proliferation and chronic inflammation, which may affect the risk for venous thromboembolism (VTE). OBJECTIVES: To examine the risk for VTE in patients with MF and parapsoriasis. METHODS: We conducted a nationwide population-based cohort study in Denmark to examine the relative risk (RR) of VTE in 525 patients with MF and 634 patients with parapsoriasis compared with that in sex- and age-matched controls from the general population. RESULTS: In patients with MF, the 10-year absolute risk for VTE was 3.4% (95% confidence interval [CI], 2.0-5.4). The adjusted RRs were 2.41 (95% CI, 1.49-3.90) for VTE and 4.01 (95% CI, 2.16-7.46) for pulmonary embolism. Notably, within the first 5 years after diagnosis with MF, the RR of pulmonary embolism was increased 6.7-fold (to 6.71 [95% CI, 2.86-15.72]). Patients with parapsoriasis had a 2.7-fold increased RR of VTE (to 2.67 [95% CI, 1.32-5.40]) in the absence of other established VTE risk factors. LIMITATIONS: We had no information regarding disease stage of MF and prescribed drugs. CONCLUSION: Patients with MF and parapsoriasis had an increased RR of VTE, although the absolute risk remained low. These findings should increase awareness of comorbidities in patients with MF and parapsoriasis.

Splanchnic venous thrombosis is a marker of cancer and a prognostic factor for cancer survival.

It is unknown if splanchnic venous thrombosis (SVT) is a marker of occult cancer and a prognostic factor for cancer survival. Using Danish medical registries, we conducted a nationwide cohort study including all patients with first-time SVT (n = 1191) between 1994 and 2011. We followed the patients for subsequent cancer diagnoses and calculated absolute risks and standardized incidence ratios (SIRs). We formed a matched comparison cohort of cancer patients without SVT, and assessed the prognostic impact of SVT on cancer survival by applying the Kaplan-Meier method and Cox regression. We followed the patients for a median of 1.6 years, and found that SVT was a marker of occult cancer. The 3-month cancer risk was 8.0% and the SIR was 33 (95% confidence interval, 27-40), compared with the general population. Increased risk was mainly found for liver cancer (risk = 3.5%; SIR = 1805), pancreatic cancer (risk = 1.5%; SIR = 256), and myeloproliferative neoplasms (risk = 0.7%; SIR = 764). The overall SIR remained increased twofold after 1 or more years of follow-up. SVT was also a prognostic factor for survival in patients with liver and pancreatic cancer. The clinical impact may be a more thorough diagnostic work-up in patients presenting with SVT.

Conisation as a marker of persistent human papilloma virus infection and risk of breast cancer.

BACKGROUND: Human papillomavirus (HPV) infection may increase breast cancer (BC) risk. METHODS: To examine this, we used nationwide medical registries to identify all Danish women who underwent conisation to remove HPV-associated cervical precancerous lesions (n=87 782) from 1978 to 2013. We computed the absolute risk of BC and standardised incidence ratios (SIRs) and 95% confidence intervals (95% CIs) for breast cancer, based on national breast cancer incidence rates. RESULTS: Conisation was associated with slightly increased BC incidence (SIR=1.1, 95% CI=1.0-1.1), and an absolute BC risk of 7.7% (95% CI=7.3-8.1%) in 35.9 years of follow-up. BC risk was elevated throughout follow-up, especially in the first 5 years (<1 year: SIR=1.2, 95% CI=0.92-1.5; 1-5 years: SIR=1.2, 95% CI=1.1-1.3; ⩾5 years: SIR=1.1, 95% CI=1.0-1.1). Women who underwent conisation and had autoimmune disease had elevated BC risk after 5 years of follow-up (SIR=1.4, 95% CI=1.0-1.8). CONCLUSIONS: BC risk is slightly elevated in women with persistent HPV infection, possibly due to detection bias.

Risk of cancer in patients with inflammatory bowel diseases: a nationwide population-based cohort study with 30 years of follow-up evaluation.

BACKGROUND & AIMS: Data regarding the risk of gastrointestinal and extraintestinal cancers in Crohn's disease (CD) and ulcerative colitis (UC) are needed to understand the clinical course of inflammatory bowel diseases (IBDs) and their treatments. METHODS: We performed a nationwide historical cohort study using Danish health care databases. We identified patients with a diagnosis of CD or UC, recorded from 1978 through 2010, and followed them up until the first occurrence of cancer, death, or emigration. We used standardized incidence ratios (SIRs) to compare cancer incidence in CD and UC patients with that expected in the general population. RESULTS: Excluding cancers diagnosed within 1 year of IBD diagnosis, 772 cases of invasive cancer occurred among 13,756 patients with CD (SIR, 1.3; 95% confidence interval [CI], 1.2-1.4) and 2331 occurred among 35,152 patients with UC (SIR, 1.1; 95% CI, 1.0-1.1). CD was associated weakly with gastrointestinal cancers (SIR, 1.2; 95% CI, 1.0-1.4) and extraintestinal cancers (SIR, 1.3; 95% CI, 1.2-1.4), with the strongest associations for hematologic malignancies (SIR, 1.9; 95% CI, 1.5-2.3), smoking-related cancers (SIR, 1.5; 95% CI, 1.3-1.8), and melanoma (SIR, 1.4; 95% CI, 1.0-1.9). Associations between UC and gastrointestinal and extraintestinal cancers were weaker (SIR, 1.1; 95% CI, 1.0-1.2; and SIR, 1.1; 95% CI, 1.0-1.1, respectively). The relative risk of extraintestinal cancers among patients with IBD was relatively stable over time, although the risk of gastrointestinal cancers decreased. CONCLUSIONS: Patients with IBD, particularly CD, are at increased risk for gastrointestinal and extraintestinal malignancies. The relative risk of gastrointestinal malignancy has decreased since 1978, without a concomitant increase in the risk of nongastrointestinal malignancy.

Renal cell carcinoma and risk of second primary cancer: A Danish nationwide cohort study.

AIM: To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). METHODS: We identified all patients diagnosed with incident RCC during 1995-2019, using population-based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population. RESULTS: The absolute 1- and 20-year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person-years (PY) (SIR, 2.3; 95% CI: 2.1-2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow-up (SIR, 1.3; 95% CI: 1.2-1.4), and 6 per 1000 PY beyond 5 years of follow-up (SIR, 1.4; 95% CI: 1.3-1.5). The sustained elevated cancer risk beyond 1 year of follow-up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006-2019 than in 1995-2005, but only during the first year of follow-up. CONCLUSION: Patients with incident RCC have a sustained 40% elevated long-term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer.

Social characteristics and social benefit use among premenopausal breast cancer survivors in Denmark: a population-based cohort study.

PURPOSE: In 2020, one million women aged < 55 years were diagnosed with breast cancer globally. The impact of breast cancer and its treatments on these women's ability to work and need for social benefits may differ by social characteristics. We evaluated social benefit use following breast cancer by education and cohabitation. METHODS: We conducted a nationwide population-based cohort study, including women aged 18-55 years diagnosed with stage I-III breast cancer in Denmark during 2002-2011. Statistics Denmark provided information on cohabitation, education, and social benefit use from 1 year pre-diagnosis to 10 years post-diagnosis. We calculated weekly proportions of self-support, unemployment, disability pension, flexi jobs, and sick leave according to education and cohabitation. RESULTS: Of 5345 women, 81.8% were self-supporting, 4.5% received disability pensions, 1.6% had flexi jobs, 3.6% were on sick leave, and 5.5% were unemployed 1 year pre-diagnosis. Ten years post-diagnosis, the proportions were 69.0%, 13.0%, 10.5%, 3.4%, and 2.0% of 3663 survivors. Disability pensions and flexi jobs increased from 12.1 to 26.4% and 2.8 to 13.5% in women with short education, from 4.1 to 12.8% and 1.8 to 12.2% in women with medium education, and from 0.8 to 6.0% and 0.9 to 6.9% in longer educated. Disability pensions increased more in women living alone (7.8 to 19.9%), than in cohabiting women (3.6 to 11.3%). CONCLUSIONS: Use of social benefits reflecting lost ability to work was highest in less educated women and in women living alone. IMPLICATIONS FOR CANCER SURVIVORS: Awareness of these groups is crucial when tailoring efforts to support work participation in cancer survivors.

Social Characteristics and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women With Breast Cancer.

PURPOSE: Social characteristics, including cohabitation/marital status and socioeconomic position (SEP)-education level, employment status, and income-influence breast cancer prognosis. We investigated the impact of these social characteristics on adherence to adjuvant endocrine therapy (AET) from treatment initiation to 5 years after diagnosis. METHODS: We assembled a nationwide, population-based cohort of premenopausal women diagnosed in Denmark with stage I-III, estrogen receptor-positive breast cancer during 2002-2011. We ascertained prediagnostic social characteristics from national registries. AET adherence was based on information from the Danish Breast Cancer Group and operationalized as (1) adherence trajectories (from group-based trajectory modeling) and (2) early discontinuation. We computed odds ratios (ORs) and associated 95% CI to estimate the association of cohabitation and SEP with AET adherence using multinomial and logistic regression models adjusted according to directed acyclic graphs. RESULTS: Among 4,353 patients, we identified three adherence trajectories-high adherence (57%), slow decline (36%), and rapid decline (6.9%). Compared with cohabiting women, those living alone had higher ORs of slow (1.26 [95% CI, 1.08 to 1.46]) or rapid decline (1.66 [95% CI, 1.27 to 2.18]) versus high adherence. The corresponding ORs for women not working versus employed women were 1.22 (95% CI, 1.02 to 1.45) and 1.76 (95% CI, 1.30 to 2.38). For early discontinuation (17%), the ORs were 1.48 (95% CI, 1.23 to 1.78) for living alone and 1.44 (95% CI, 1.17 to 1.78) for women not working. CONCLUSION: Adherence to AET was lower among women living alone or unemployed than cohabiting or employed women, respectively. These women may benefit from support programs to enhance AET adherence.

Lymph node enlargement and risk of haematological and solid cancer.

Enlarged lymph nodes may be a marker of occult cancer, but accurate data on cancer risk are limited. We used population-based Danish medical registries to assess cancer risk in a cohort of patients with a first-time inpatient or outpatient hospital contact for enlarged lymph nodes during 1994-2008. Observed cancer incidences were compared with that expected in the general population. We observed 1750 cancers among 11284 patients with enlarged lymph nodes during median follow up of 4.7 years. Only 389 cases were expected. Cancer risk was 11.5% [95% confidence interval (CI): 10.9-12.1%] during the first year of follow up, corresponding to an age- and sex-standardized incidence ratio (SIR) of 21.1 (95% CI: 20.0-22.3). One-year SIRs were more than 100 times increased for head and neck cancer and lymphomas. Beyond one year of follow up, overall cancer risk remained 1.4-fold (95% CI: 1.3-1.5-fold) higher than expected, while risk of lymphoma remained six to 10 times higher. Cancer risk was also elevated among patients with other conditions known to be associated with enlarged lymph nodes, such as infections and rheumatic disorders. We conclude that enlarged lymph nodes are a marker of occult cancer and long-term risk of cancer.

Long-term clinical outcomes of patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study.

Few data exist on the long-term prognosis of patients with chronic primary chronic immune thrombocytopenia (ITP). We examined the risk of infections, hemorrhage resulting in hospitalization, hematologic malignancies, and total and cause-specific mortality among patients with ITP compared with the general population. We used population-based medical databases to identify 407 patients with primary chronic ITP diagnosed during 1996 to 2007 and 4069 general population members individually matched on age, sex, and comorbidity level. We used Cox regression analysis to estimate rate ratios (RRs) adjusted for age (≤ 60 or > 60 years), sex, calendar year, and level of comorbidity. The adjusted 1-year RR of infection was 4.5 (95% confidence interval [CI], 3.3-6.1) for patients with chronic ITP compared with the general population cohort. The adjusted RR decreased to 1.8 (95% CI, 1.3-2.5) for the second to fifth year of follow-up. The adjusted 5-year RR was 3.2 (95% CI, 1.2-9.0) for hospitalized intracranial hemorrhage, 4.4 (95% CI, 2.3-8.3) for other hospitalized hemorrhages, and 4.7 (95% CI, 1.7-12.7) for hematologic malignancy. The 5-year all-cause mortality RR was 2.3 (95% CI, 1.8-3.0). In summary, primary chronic ITP was associated with substantially increased long-term risk of infections, hemorrhagic episodes requiring hospitalization, hematologic malignancies, and mortality.

Risk of primary haematologic cancers following incident non-metastatic breast cancer: A Danish population-based cohort study.

BACKGROUND: Breast cancer survivors may have increased risk of subsequent haematologic cancer. We compared their risk of haematologic cancers with the general population during 38 years of follow-up. METHODS: Using population-based Danish medical registries, we assembled a nationwide cohort of women diagnosed with incident non-metastatic breast cancer during 1980-2017, with follow-up through 2018. We compared breast cancer survivors with the general population by computing standardised incidence ratios (SIR) and 95% confidence intervals (CI). RESULTS: Among 101,117 breast cancer survivors, we observed 815 incident haematologic cancers (median follow-up: 7.9 years). We observed excess risk of acute myeloid leukaemia (AML) (SIR: 1.65, 95%CI: 1.33-2.01), particularly in women who received chemotherapy (SIR: 3.33, 95%CI: 2.24-4.75) and premenopausal women (SIR: 3.23, 95%CI: 2.41-4.25). The risk of acute lymphoid leukaemia (ALL) was increased (SIR: 2.25, 95%CI: 1.29-3.66), whereas the risk of chronic lymphoid leukaemia (CLL) was decreased (SIR: 0.66, 95%CI: 0.53-0.82). An additional analysis showed elevated risk of CLL 0-6 months after breast cancer diagnosis (SIR: 3.00 95%CI: 1.75-4.80). CONCLUSION: Compared to the general population, breast cancer survivors had elevated risk of AML, particularly when treated with chemotherapy. The risk of ALL was elevated, whereas the risk of CLL was lower. The higher risk of CLL in the first six months after diagnosis likely reflects surveillance bias-due to intensified diagnostic efforts at breast cancer diagnosis and treatment-prompting earlier detection. This has likely reduced the long-term risk of CLL in breast cancer survivors.

Erosive reflux disease increases risk for esophageal adenocarcinoma, compared with nonerosive reflux.

BACKGROUND & AIMS: Gastroesophageal reflux disease is a strong risk factor for esophageal adenocarcinoma, but it is not clear whether the mucosal inflammation that develops in patients with reflux disease promotes this cancer. We determined the development of adenocarcinoma among patients who underwent esophagogastroduodenoscopy and were found to have erosive (with esophagitis) or nonerosive (without esophagitis) reflux. METHODS: We performed a nationwide cohort study using data from 33,849 patients with reflux disease (52% men; median age, 59.3 y) from population-based Danish medical registries, from 1996 through 2008. The observed incidences of adenocarcinoma were compared with the expected incidence for the general population, standardized by age, sex, and calendar time. Absolute risks were estimated using Kaplan-Meier methods. RESULTS: In the study cohort, 26,194 of the patients (77%) had erosive reflux disease and 37 subsequently developed esophageal adenocarcinoma after a mean follow-up time of 7.4 years. Their absolute risk after 10 years was 0.24% (95% confidence interval [CI], 0.15%-0.32%). The incidence of cancer among patients with erosive reflux disease was significantly greater than that expected for the general population (standardized incidence ratio, 2.2; 95% CI, 1.6-3.0). In contrast, of the 7655 patients with nonerosive reflux disease, only 1 was diagnosed with esophageal adenocarcinoma after 4.5 years of follow-up evaluation (standardized incidence ratio, 0.3; 95% CI, 0.01-1.5). CONCLUSIONS: Erosive reflux disease, but not nonerosive disease, increased the risk of esophageal adenocarcinoma, based on analysis of population-based Danish medical registries. Inflammation therefore might be an important factor in the progression from reflux to esophageal adenocarcinoma.

Fever of Unknown Origin: A Validation Study of Danish ICD-10 Diagnosis Codes.

Background: Real-world data in form of routinely collected clinical data are a valuable resource for epidemiological research in infectious disease. We examined the validity of a discharge diagnosis of fever of unknown origin from hospital discharge registries. Methods: We identified patients with a first in- or outpatient diagnosis (primary or secondary) of fever of unknown origin (ICD-10 code R50.0; R50.8, R50.9) recorded in the Danish National Patient Registry (DNPR) between 2010 and 2017 in the North Denmark Region. We based the validation cohort on a mix of patients diagnosed at a highly specialized university department of infectious diseases (n=100), other internal medicine departments (n=50), and patients diagnosed at a regional non-university hospital (n=50). We estimate positive predictive value (PPV) of diagnosis for fever of unknown origin using medical records as reference. Results: The PPV of a diagnosis of fever of unknown origin for patients diagnosed at the infectious disease department was 61% (95% CI: 51-71%). For other internal medicine departments, it was 14% (95% CI: 6-27%), and for the non-university hospital it was 16% (95% CI: 7-29%). To achieve higher PPVs, we excluded immunocompromised patients, patients who were diagnosed with infection, cancer or rheumatic disease within 7 days after admission, and/or patients with a short hospital stay (maximum 3 days) and no subsequent hospital contact within 1 month. The PPV for diagnoses from the Department of Infectious Diseases improved to 82% (95% CI: 68-91%) for other internal medicine departments it improved to 31% (95% CI: 11-59%), and for the non-university hospital it improved to 36% (95% CI: 13-65%). Conclusion: We found that only diagnoses made in the Department of Infectious Diseases accurately identified fever of unknown origin, whereas diagnoses made in other units mainly covered infection-related fever, cancer-related fever, or short unspecific fever without further diagnostic work-up.