Immune checkpoint inhibitor treatment and ophthalmologist consultations in patients with malignant melanoma or lung cancer—A nationwide cohort study

SIMPLE SUMMARY: Immune checkpoint inhibitors are increasingly being used for treating advanced malignant cutaneous melanoma and lung cancer. Immune-related side effects in multiple organs are common but the frequencies of ophthalmic side effects in national cohorts of unselected patients are undescribed. This study estimated frequencies of first-time ophthalmologist consultations and inflammatory conditions in consecutive patients with malignant melanoma or lung cancer treated with immune checkpoint inhibitors in Denmark from 2011–2018. The one-year risks of first-time consultation and ocular inflammation were 6% and 1%, respectively. These numbers were increased compared with patients with the same type of cancer who were not treated with immune checkpoint inhibitiors. ABSTRACT: Purpose: To estimate the frequency of first-time ocular events in patients treated with immune checkpoint inhibitors (ICI). Methods: Patients with cancer in 2011–2018 in Denmark were included and followed. The outcomes were first-time ophthalmologist consultation and ocular inflammation. One-year absolute risks of outcomes and hazard ratios were estimated. Results: 112,289 patients with cancer were included, and 2195 were treated with ICI. One year after the first ICI treatment, 6% of the patients with cancer, 5% and 8% of the lung cancer (LC) and malignant cutaneous melanoma (MM) patients, respectively, had a first-time ophthalmologist consultation. The risk of ocular inflammation was 1% (95% confidence interval (CI) 0.4–1.2). Among patients with MM, ICI was associated with ocular inflammation in women (HR 12.6 (95% CI 5.83–27.31) and men (4.87 (95% CI 1.79–13.29)). Comparing patients with and without ICI treatment, the risk of first-time ophthalmologist consultation was increased in patients with LC (HR 1.74 (95% CI 1.29–2.34) and MM (HR 3.21 (95% CI 2.31–4.44). Conclusions: The one-year risks of first-time ophthalmologist consultation and ocular inflammation were 6% and 1%, respectively, in patients treated with ICI. In patients with LC and MM, the risk was increased in patients with ICI compared with patients without ICI

Prediction of first cardiovascular disease event in 2.9 million individuals using Danish administrative healthcare data:a nationwide, registry-based derivation and validation study

AIMS: The aim of this study was to derive and validate a risk prediction model with nationwide coverage to predict the individual and population-level risk of cardiovascular disease (CVD). METHODS AND RESULTS: All 2.98 million Danish residents aged 30–85 years free of CVD were included on 1 January 2014 and followed through 31 December 2018 using nationwide administrative healthcare registries. Model predictors and outcome were pre-specified. Predictors were age, sex, education, use of antithrombotic, blood pressure-lowering, glucose-lowering, or lipid-lowering drugs, and a smoking proxy of smoking-cessation drug use or chronic obstructive pulmonary disease. Outcome was 5-year risk of first CVD event, a combination of ischaemic heart disease, heart failure, peripheral artery disease, stroke, or cardiovascular death. Predictions were computed using cause-specific Cox regression models. The final model fitted in the full data was internally-externally validated in each Danish Region. The model was well-calibrated in all regions. Area under the receiver operating characteristic curve (AUC) and Brier scores ranged from 76.3% to 79.6% and 3.3 to 4.4. The model was superior to an age-sex benchmark model with differences in AUC and Brier scores ranging from 1.2% to 1.5% and −0.02 to −0.03. Average predicted risks in each Danish municipality ranged from 2.8% to 5.9%. Predicted risks for a 66-year old ranged from 2.6% to 25.3%. Personalized predicted risks across ages 30–85 were presented in an online calculator (https://hjerteforeningen.shinyapps.io/cvd-risk-manuscript/). CONCLUSION: A CVD risk prediction model based solely on nationwide administrative registry data provided accurate prediction of personal and population-level 5-year first CVD event risk in the Danish population. This may inform clinical and public health primary prevention efforts

Incidence of new onset cancer in patients with a myocardial infarction – a nationwide cohort study

Abstract Background Few studies have suggested that patients with myocardial infarction (MI) may be at increased risk of cancer, but further large register-based studies are needed to evaluate this subject. The aim of this study was to assess the incident rates of cancer and death by history of MI, and whether an MI is independently associated with cancer in a large cohort study. Method All Danish residents aged 30–99 in 1996 without prior cancer or MI were included and were followed until 2012. Patients were grouped according to incident MI during follow-up. Incidence rates (IR) of cancer and death in individuals with and without MI and incidence rate ratios (IRR, using multivariable Poisson regression analyses) of cancer associated with an MI were calculated. Results Of 2,871,168 individuals, 122,275 developed an MI during follow-up, 11,375 subsequently developed cancer (9.3%, IR 19.1/1000 person-years) and 65,225 died (53.3%, IR 106.0/1000 person-years). In the reference population, 372,397 developed cancer (13.0%, IR 9.3/1000 person-years) and 753,767 died (26.3%, IR 18.2/1000 person-years). Compared to the reference population, higher IRs of cancer and death were observed in all age groups (30–54, 55–69 and 70–99 years) and time since an MI (0–1, 1–5 and 5–17 years) in the MI population. MI was associated with an increased risk of overall cancer (IRR 1.14, 95% CI 1.10–1.19) after adjusting for age, sex and calendar year, also when additionally adjusting for chronic obstructive pulmonary disease, hypertension, dyslipidemia, diabetes and socioeconomic status (IRR 1.08, 95% CI 1.03–1.13), but not after further adjustment for the first 6 months post-MI (IRR 1.00, 95% CI 0.96–1.05). Conclusion Patients after an MI have increased incidence of cancer, which may be explained by mutual risk, occult cancers and increased surveillance. Focus on risk factor management to reduce cancer and MI is warranted