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Aim To determine whether mortality for patients with diffuse large B‐cell lymphoma who survived 5 years (DLBCL5ys) returns thereafter to general population levels. Methods This population‐based cohort study included Danish residents between January 1, 2000, and December 31, 2023. Information on diagnoses, comorbidities, and vital status came from Danish health and administrative registries. Analyses included 4164 DLBCL5yr patients—55% of incident patients—and 41,640 individuals from the general population matched 10:1 by exact birth year, sex, and the calendar year of achieving DLBCL5yr status. We used Cox proportional hazards models to compute matched mortality hazard ratios (HRs) and 95% confidence intervals (CIs) and controlled for comorbidities by adding Charlson comorbidity index scores to our models. Results Mortality rates were elevated for DLBCL5yr patients soon after their 5‐year survival date. The absolute difference in mortality was 20 deaths per 1000 person‐years, and the HR adjusted for comorbidities was 1.5 (95% CI 1.4–1.6). Mortality was elevated similarly for men and women. The elevated mortality for DLBCL5yr patients varied in magnitude by age, calendar period, and comorbidity burden, and included excess mortality from DLBCL, cancers other than lymphoma, and respiratory diseases. Conclusions We found that mortality for DLBCL5yr patients did not return to general population levels.

Venous thromboembolism may be a harbinger of cancer. Patients with diverticular disease are suggested to have an increased risk of developing venous thromboembolism compared with the general population, but it remains unclear whether venous thromboembolism is also a marker of occult cancer in these patients. We investigated the risk of cancer after venous thromboembolism among patients with diverticular disease. We used Danish health registries to conduct a nationwide, population-based cohort study during 1996-2017. We identified all venous thromboembolism patients with a diagnosis of diverticular disease and calculated absolute risks of cancer and standardized incidence ratios (SIRs) by comparing observed and expected cancer incidence based on national cancer incidence in the Danish population. We followed 3406 patients with venous thromboembolism and diverticular disease for a median of 3.0 years (interquartile range: 1.0-6.0). During the first year of follow-up, we observed 212 cancer cases. The corresponding one-year risk of cancer was 6.2% (95% confidence interval [CI]: 5.5-7.1) with a SIR of 2.9 (95% CI: 2.5-3.3). The SIRs were particularly elevated for cancers of the stomach, pancreas, ovary, and kidney. During the second and subsequent years of follow-up, 337 cancers were diagnosed with a SIR of 1.1 (95% CI: 1.0-1.3). Venous thromboembolism is a harbinger of occult cancer in patients with diverticular disease.

Cancer may increase the risk of bleeding. However, whether subdural hematoma is a marker of occult cancer remains unknown. We examined the association between non-traumatic subdural hematoma and cancer risk in a cohort study. Using Danish nationwide health registries, we identified 2713 patients with non-traumatic subdural hematoma and no previous cancer diagnosis, who were hospitalized between April 1, 1996 and December 31, 2019. We computed age-, sex-, and calendar year-standardized incidence ratios (SIRs) as the ratio of the observed to expected number of patients with cancer by using national incidence rates as reference as a measure of relative risk. We identified 77 cancer cases within the first year of follow-up and 272 cancer cases thereafter. The one-year risk of cancer was 2.8% (95% confidence interval: 2.2-3.5), and the one-year SIR was 1.7 (95% confidence interval: 1.3-2.1). During the subsequent years, the SIR was 1.0 (95% confidence interval: 0.9-1.1). The relative risk was elevated for some hematological and liver cancers. The risk of a new cancer diagnosis was clearly increased in patients with non-traumatic subdural hematoma compared with the general population during the first year of follow-up. However, the absolute risk was low, thus limiting the clinical relevance of pursuing early cancer detection in these patients.

Abstract Context Thyroid nodules, adenomas, and goiter have consistently been associated with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction and thyroid autoimmunity influence this risk. Objective To examine thyroid cancer risk after diagnoses of a wide range of benign thyroid conditions. Design Hospital and cancer registry linkage cohort study for the years 1978 to 2013. Setting Nationwide (Denmark). Participants Patients diagnosed with hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n = 12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582), other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807 residents of Denmark during the study period. Main Outcome Measures We computed standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding the first 12 months of follow-up after benign thyroid disease diagnosis. Results SIRs were significantly elevated for all benign thyroid diseases apart from hypothyroidism. SIRs were higher for men than women and in the earlier follow-up periods. Elevated SIRs were observed for localized and regional/distant thyroid cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27 thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92], nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to 11.5) remained positively associated with thyroid cancer risk. Conclusions We found an unexpected increased risk of differentiated thyroid cancer, including regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis that could not be solely attributed to increased medical surveillance. Hypothyroidism was less clearly associated with thyroid cancer risk. This large nationwide study provides strong evidence for an increased risk of differentiated thyroid cancer following diagnosis of hyperthyroidism and thyroiditis.

ObjectiveAspirin may increase the risk of lower gastrointestinal bleeding (LGIB) from precursors of colorectal cancer (CRC). We investigated whether use of low-dose aspirin, through initiation of LGIB, may lead patients to undergo colonoscopy and polypectomy before manifest CRC.DesignWe conducted a historical cohort study (2005–2013) of all Danish residents who initiated low-dose aspirin treatment (n=412 202) in a setting without screening for CRC. Each new aspirin user was matched with three non-users (n=1 236 560) by age, sex and region of residence on the date of their matched new user’s first-time aspirin prescription (index date). We computed absolute risks (ARs), risk differences and relative risks (RRs) of LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC, comparing aspirin users with non-users.ResultsThe ARs were higher for new users than non-users for LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC within 3 months after index. Comparing new users with non-users, the RRs were 2.79 (95% CI 2.40 to 3.24) for LGIB, 1.73 (95% CI 1.63 to 1.84) for lower gastrointestinal endoscopy, 1.56 (95% CI 1.42 to 1.72) for colorectal polyps and 1.73 (95% CI 1.51 to 1.98) for CRC. The RRs remained elevated for more than 12 months after the index date, with the exception of CRC where the RRs were slightly decreased during the 3–5 years (RR 0.90, 95% CI 0.83 to 0.98) and more than 5 years (RR 0.91, 95% CI 0.82 to 1.00) following the index date.ConclusionThese findings indicate that aspirin may contribute to reduce CRC risk by causing premalignant polyps to bleed, thereby expediting colonoscopy and polypectomy before CRC development.

Background: Multiple sclerosis (MS) patients may be at increased risk of venous thromboembolism (VTE), but evidence is limited. Objectives: To examine long-term risk of VTE among MS patients. Patients and Methods: We conducted a population-based cohort study among 17,418 Danish MS patients and 87,090 comparison cohort members from the general population. Data on MS, VTE and comorbidities were obtained from the Danish National Registry of Patients including all admissions to Danish hospitals since 1977. We computed cumulative risks for VTE and adjusted incidence rate ratios (IRRs). Results: A total of 34 (0.2%) MS patients and 36 (0.04%) comparison cohort members had a deep venous thrombosis (DVT) within 1 year following the date of initial MS diagnosis/index date [adjusted IRR = 3.02 (95% CI: 2.14–4.27)]. During this period, 16 (0.09%) MS patients and 26 (0.03%) comparison cohort members had a documented pulmonary embolism (PE) [adjusted IRR = 2.85 (95% CI: 1.72–4.70)]. During the subsequent up to 29 years, 315 (1.9% of MS patients alive at year 1) MS patients had a record of a DVT [adjusted IRR = 2.28 (95% CI: 2.01–2.59)] and 129 (0.8%) had PE [IRR = 1.58 (95% CI: 1.31–1.92]. Conclusion: MS is a risk factor for VTE, but the absolute risk is low.

Abstract Context Acromegaly has been associated with increased risk of cancer morbidity and mortality, but research findings remain conflicting and population-based data are scarce. We therefore examined whether patients with acromegaly are at higher risk of cancer. Design A nationwide cohort study (1978 to 2010) including 529 acromegaly cases was performed. Incident cancer diagnoses and mortality were compared with national rates estimating standardized incidence ratios (SIRs). A meta-analysis of cancer SIRs from 23 studies (including the present one) was performed. Results The cohort study identified 81 cases of cancer after exclusion of cases diagnosed within the first year [SIR 1.1; 95% confidence interval (CI), 0.9 to 1.4]. SIRs were 1.4 (95% CI, 0.7 to 2.6) for colorectal cancer, 1.1 (95% CI, 0.5 to 2.1) for breast cancer, and 1.4 (95% CI, 0.6 to 2.6) for prostate cancer. Whereas overall mortality was elevated in acromegaly (SIR 1.3; 95% CI, 1.1 to 1.6), cancer-specific mortality was not. The meta-analysis yielded an SIR of overall cancer of 1.5 (95% CI, 1.2 to 1.8). SIRs were elevated for colorectal cancer, 2.6 (95% CI, 1.7 to 4.0); thyroid cancer, 9.2 (95% CI, 4.2 to 19.9); breast cancer, 1.6 (1.1 to 2.3); gastric cancer, 2.0 (95% CI, 1.4 to 2.9); and urinary tract cancer, 1.5 (95% CI, 1.0 to 2.3). In general, cancer SIR was higher in single-center studies and in studies with <10 cancer cases. Conclusions Cancer incidence rates were slightly elevated in patients with acromegaly in our study, and this finding was supported by the meta-analysis of 23 studies, although it also suggested the presence of selection bias in some earlier studies. A population-based study and a meta-analysis of the association between acromegaly and cancer revealed a slightly elevated risk but also evidence of selection bias.

ObjectiveWe examined the risk of primary gastrointestinal cancers in women with breast cancer and compared this risk with that of the general population.DesignUsing population-based Danish registries, we conducted a cohort study of women with incident non-metastatic breast cancer (1990–2017). We computed cumulative cancer incidences and standardised incidence ratios (SIRs).ResultsAmong 84 972 patients with breast cancer, we observed 2340 gastrointestinal cancers. After 20 years of follow-up, the cumulative incidence of gastrointestinal cancers was 4%, driven mainly by colon cancers. Only risk of stomach cancer was continually increased beyond 1 year following breast cancer. The SIR for colon cancer was neutral during 2–5 years of follow-up and approximately 1.2-fold increased thereafter. For cancer of the oesophagus, the SIR was increased only during 6–10 years. There was a weak association with pancreas cancer beyond 10 years. Between 1990–2006 and 2007–2017, the 1–10 years SIR estimate decreased and reached unity for upper gastrointestinal cancers (oesophagus, stomach, and small intestine). For lower gastrointestinal cancers (colon, rectum, and anal canal), the SIR estimate was increased only after 2007. No temporal effects were observed for the remaining gastrointestinal cancers. Treatment effects were negligible.ConclusionBreast cancer survivors were at increased risk of oesophagus and stomach cancer, but only before 2007. The risk of colon cancer was increased, but only after 2007.

Importance The burden of caring for children with complex medical problems such as major congenital anomalies falls principally on mothers, who in turn suffer a variety of potentially severe economic consequences. As well, health consequences of caregiving often further impact the social and economic prospects of mothers of children with major congenital anomalies (MCMCAs). Evaluating the long-term economic consequences of extensive in-home caregiving among MCMCAs can inform strategies to mitigate these effects. Objective To assess whether MCMCAs face reduced employment and increased need for disability benefits over a 20-year period. Design A population-based matched cohort study. Setting Denmark. Participants All women who gave birth to a singleton child with a major congenital anomaly in Denmark between January 1, 1997 and December 31, 2017 ( n  = 23,637) and a comparison cohort of mothers matched by maternal age, parity, and infant’s year of birth ( n  = 234,586). Exposures Liveborn infant with a major congenital anomaly. Main outcomes and measures The primary outcome was mothers’ employment status, stratified by their child’s age. Employment status was categorized as employed, outside the workforce (on temporary leave, holding a flexible job, or pursuing education), or unemployed; the number of weeks in each category was measured over time. The secondary outcome was time to receipt of a disability pension, which in Denmark implies permanent exit from the labor market. We used a negative binomial regression model to estimate the number of weeks in each employment category, stratified by the child’s age ( i.e., 0–1 year, > 1–6 years, 7–13 years, 14–18 years). A Cox proportional hazards regression model was used to compute hazard ratios as a measure of the relative risk of receiving a disability pension. Rate ratios and hazard ratios were adjusted for maternal demographics, pregnancy history, health, and infant’s year of birth. Results During 1–6 years after delivery, MCMCAs were outside the workforce for a median of 50 weeks (IQR, 6–107 weeks), while members of the comparison cohort were outside the workforce for a median of 48 weeks (IQR, 4–98 weeks), corresponding to an adjusted rate ratio [ARR] of 1.05 (95% confidence interval [CI], 1.04–1.07). During the first year after delivery, MCMCAs were more likely to be employed than mothers in the comparison cohort (ARR, 1.08; 95% CI, 1.06–1.10). At all timepoints thereafter, MCMCAs had a lower rate of workforce participation. The rate of being outside the workforce was 5% higher than mothers in the comparison cohort during 1–6 years after delivery (ARR, 1.05; 95% CI, 1.04–1.07), 9% higher during 7–13 years after delivery (ARR, 1.09; 95% CI, 1.06–1.12), and 12% higher during 14–18 years after delivery (ARR, 1.12; 95% CI, 1.07–1.18). Overall, MCMCAs had a 20% increased risk of receiving a disability pension during follow-up than mothers in the matched comparison cohort [incidence rates 3.10 per 1000 person-years (95% CI, 2.89–3.32) vs. 2.34 per 1000 person-years (95% CI, 2.29–2.40), adjusted hazard ratio, 1.20; 95% CI, 1.11–1.29]. Conclusion and relevance MCMCAs were less likely to participate in the Danish workforce, less likely to be employed, and more likely to receive disability pensions than mothers of unaffected children. The rate of leaving the workforce intensified as their affected children grew older. The high demands of caregiving among MCMCAs may have long-term employment consequences even in nations with comprehensive and heavily tax-supported childcare systems, such as Denmark.

BACKGROUND:It is unknown whether posttraumatic stress disorder (PTSD) is associated with incident infections. This study’s objectives were to examine (1) the association between PTSD diagnosis and 28 types of infections and (2) the interaction between PTSD diagnosis and sex on the rate of infections. METHODS:The study population consisted of a longitudinal nationwide cohort of all residents of Denmark who received a PTSD diagnosis between 1995 and 2011, and an age- and sex-matched general population comparison cohort. We fit Cox proportional hazards regression models to examine associations between PTSD diagnosis and infections. To account for multiple estimation, we adjusted the hazard ratios (HRs) using semi-Bayes shrinkage. We calculated interaction contrasts to assess the presence of interaction between PTSD diagnosis and sex. RESULTS:After semi-Bayes shrinkage, the HR for any type of infection was 1.8 (95% confidence interval1.6, 2.0), adjusting for marital status, non-psychiatric comorbidity, and diagnoses of substance abuse, substance dependence, and depression. The association between PTSD diagnosis and some infections (e.g., urinary tract infections) were stronger among women, whereas other associations were stronger among men (e.g., skin infections). CONCLUSIONS:This study’s findings suggest that PTSD diagnosis is a risk factor for numerous infection types and that the associations between PTSD diagnosis and infections are modified by sex.