Psoriasis: Comorbidity and Treatment

Psoriasis is universal in occurrence, although the worldwide prevalence varies between 0.6% and 4.8%.The prevalence of psoriasis in people of Caucasian descend is approximately 2%. In the Netherlands it is therefore estimated that approximately 300,000 people are diagnosed as having psoriasis. Its prevalence is equal in men and women and can first appear at any age, from infancy to elderly, although the mean age of development has suggested to be around 30 years old. Some studies suggest the presence of two forms of psoriasis related to the age at onset. Early onset psoriasis, which comprises approximately 75% of the psoriasis population, presents itself before the age of 40 mostly with a positive family history and with more severe disease. While late onset psoriasis presents itself after the age of 40 and may have a less severe clinical course. However, other studies were not able to confirm the presence of more severe psoriasis in those subjects with an early age of onset. The extent of body surface area affected by psoriasis is variable, but in most people the severity of their psoriasis is reasonably stable over time. Based on a patient survey the prevalence of moderate to severe psoriasis (i.e. more than 3% of the body surface area affected) was recently estimated to be approximately 17%

Predicting keratinocyte carcinoma in patients with actinic keratosis: development and internal validation of a multivariable risk-prediction model

Background: Patients with actinic keratosis (AK) are at increased risk for developing keratinocyte carcinoma (KC) but predictive factors and their risk rates are unknown. Objectives: To develop and internally validate a prediction model to calculate the absolute risk of a first KC in patients with AK. Methods: The risk-prediction model was based on the prospective population-based Rotterdam Study cohort. We hereto analysed the data of participants with at least one AK lesion at cohort baseline using a multivariable Cox proportional hazards model and included 13 a priori defined candidate predictor variables considering phenotypic, genetic and lifestyle risk factors. KCs were identified by linkage of the data with the Dutch Pathology Registry. Results: Of the 1169 AK participants at baseline, 176 (15·1%) developed a KC after a median follow-up of 1·8 years. The final model with significant predictors was obtained after backward stepwise selection and comprised the presence of four to nine AKs [hazard ratio (HR) 1·68, 95% confidence interval (CI) 1·17–2·42], 10 or more AKs (HR 2·44, 95% CI 1·65–3·61), AK localization on the upper extremities (HR 0·75, 95% CI 0·52–1·08) or elsewhere except the head (HR 1·40, 95% CI 0·98–2·01) and coffee consumption (HR 0·92, 95% CI 0·84–1·01). Evaluat

Weighted metrics are required when evaluating the performance of prediction models in nested case–control studies

Background: Nested case–control (NCC) designs are efficient for developing and validating prediction models that use expensive or difficult-to-obtain predictors, especially when the outcome is rare. Previous research has focused on how to develop prediction models in this sampling design, but little attention has been given to model validation in this context. We therefore aimed to systematically characterize the key elements for the correct evaluation of the performance of prediction models in NCC data. Methods: We proposed how to correctly evaluate prediction models in NCC data, by adjusting performance metrics with sampling weights to account for the NCC sampling. We included in this study the C-index, threshold-based metrics, Observed-to-expected events ratio (O/E ratio), calibration slope, and decision curve analysis. We illustrated the proposed metrics with a validation of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in data from the population-based Rotterdam study. We compared the metrics obtained in the full cohort with those obtained in NCC datasets sampled from the Rotterdam study, with and without a matched design. Results: Performance metrics without weight adjustment were biased: the unweighted C-index in NCC datasets was 0.61 (0.58–0.63) for the unmatched design, while the C-index in the full cohort and the weighted C-index in the NCC datasets were similar: 0.65 (0.62–0.69) and 0.65 (0.61–0.69), respectively. The unweighted O/E ratio was 18.38 (17.67–19.06) in the NCC datasets, while it was 1.69 (1.42–1.93) in the full cohort and its weighted version in the NCC datasets was 1.68 (1.53–1.84). Similarly, weighted adjustments of threshold-based metrics and net benefit for decision curves were unbiased estimates of the corresponding metrics in the full cohort, while the corresponding unweighted metrics were biased. In the matched design, the bias of the unweighted metrics was larger, but it could also be compensated by the weight adjustment. Conclusions: Nested case–control studies are an efficient solution for evaluating the performance of prediction models that use expensive or difficult-to-obtain biomarkers, especially when the outcome is rare, but the performance metrics need to be adjusted to the sampling procedure.</p

Health‐related quality of life in survivors of advanced melanoma treated with anti‐PD1‐based immune checkpoint inhibitors

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma but are associated with immune-related adverse events (irAEs). This single center, cross-sectional survey aimed to describe the long-term symptom burden and impact on health-related quality of life (HRQL) of advanced melanoma patients with sustained disease control following treatment with ICIs. Methods: Advanced melanoma patients (stage IIB, III or IV, AJCCv8), treated with anti-PD1-based ICIs, who were off-treatment and had at least 6 months follow-up from their last infusion with an ongoing response in the metastatic setting or no evidence of disease recurrence in the adjuvant setting. A paper-based questionnaire, consisting of the EORTC QLQ-C30, EORTC QLQ-FA12, and the PRO-CTCAE was administered. Results: Of 90 participants, 61 (68%) completed the questionnaire; 40 received single-agent anti-PD1, and 21 anti-PD1/anti-CTLA4. Thirty-three (54%) were treated in the adjuvant setting. At the time of enrolment, 31 (51%) participants had active treatment for a previous irAE. Overall, 18/61 (30%) participants reported long-term symptoms and trouble in physical and emotional functioning. Physical fatigue was common and interfered with daily activities (n = 12, 20%). In the PRO-CTCAE questionnaire, muscle ache (n = 12, 20%) and joint ache (n = 9, 15%) were commonly reported. Despite this, participants reported overall good health (6.00, range 2.00-7.00) and reasonable level of HRQL (6.00, range 3.00-7.00). Discussion: Melanoma survivors experience long-term symptoms in physical and psychosocial HRQL domains after ICI treatment. These results underline the importance to address existing gaps in survivorship care, implement these findings in clinical practice and increase awareness for long-term symptoms in these patients

Weighted metrics are required when evaluating the performance of prediction models in nested case–control studies

Background: Nested case–control (NCC) designs are efficient for developing and validating prediction models that use expensive or difficult-to-obtain predictors, especially when the outcome is rare. Previous research has focused on how to develop prediction models in this sampling design, but little attention has been given to model validation in this context. We therefore aimed to systematically characterize the key elements for the correct evaluation of the performance of prediction models in NCC data. Methods: We proposed how to correctly evaluate prediction models in NCC data, by adjusting performance metrics with sampling weights to account for the NCC sampling. We included in this study the C-index, threshold-based metrics, Observed-to-expected events ratio (O/E ratio), calibration slope, and decision curve analysis. We illustrated the proposed metrics with a validation of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in data from the population-based Rotterdam study. We compared the metrics obtained in the full cohort with those obtained in NCC datasets sampled from the Rotterdam study, with and without a matched design. Results: Performance metrics without weight adjustment were biased: the unweighted C-index in NCC datasets was 0.61 (0.58–0.63) for the unmatched design, while the C-index in the full cohort and the weighted C-index in the NCC datasets were similar: 0.65 (0.62–0.69) and 0.65 (0.61–0.69), respectively. The unweighted O/E ratio was 18.38 (17.67–19.06) in the NCC datasets, while it was 1.69 (1.42–1.93) in the full cohort and its weighted version in the NCC datasets was 1.68 (1.53–1.84). Similarly, weighted adjustments of threshold-based metrics and net benefit for decision curves were unbiased estimates of the corresponding metrics in the full cohort, while the corresponding unweighted metrics were biased. In the matched design, the bias of the unweighted metrics was larger, but it could also be compensated by the weight adjustment. Conclusions: Nested case–control studies are an efficient solution for evaluating the performance of prediction models that use expensive or difficult-to-obtain biomarkers, especially when the outcome is rare, but the performance metrics need to be adjusted to the sampling procedure.</p

Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies:A nationwide cohort study

Background: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. Objective: To investigate the cumulative incidence and timing of subsequent cSCCs. Methods: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. Results: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. Limitations: Only histopathologically confirmed cSCCs were included. Conclusion: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.</p

Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies:A nationwide cohort study

Background: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. Objective: To investigate the cumulative incidence and timing of subsequent cSCCs. Methods: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. Results: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. Limitations: Only histopathologically confirmed cSCCs were included. Conclusion: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.</p