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

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

Increased prevalence of advanced liver fibrosis in patients with psoriasis: A cross-sectional analysis from the rotterdam study

Prevalence of non-alcoholic fatty liver disease is increased in patients with psoriasis. However, it is not known how liver fibrosis correlates with psoriasis. This study investigated the association between psoriasis and liver fibrosis compared with participants without psoriasis within the population-based Rotterdam Study. All participants were screened for liver fibrosis using transient elastography. Liver stiffness > 9.5 kPa suggested advanced liver fibrosis. Psoriasis was identified using a validated algorithm. A total of 1,535 participants were included (mean age ± standard deviation 70.5 ± 7.9 years; 50.8% female; median body mass index 26.4 kg/ m2 (interquartile range 24.2–28.9)) of whom 74 (4.7%) had psoriasis. Prevalence of advanced liver fibrosis was 8.1% in psoriasis patients compared with 3.6% in the reference group (p = 0.05). The risk of advanced liver fibrosis in psoriasis patients remained comparable after adjustment for demographics, lifestyle characteristics and laboratory findings (odds ratio 2.57 (95% confidence interval 1.00–6.63). This study suggests that elderly people with psoriasis are twice as likely to have advanced liver fibrosis irrespective of common risk factors

Complex skin cancer treatment requiring reconstructive plastic surgery: an interview study on the experiences and needs of patients

To provide patient-centered care, it is essential to explore what patients consider important and to adjust care accordingly. This may specifically be relevant for patients with complex skin cancer, for whom the care process is often more complicated and psychological and social problems may play a larger role. The objective was to explore the experiences and needs of patients who had undergone surgical treatment by a dermatologist for a complex skin cancer with a subsequent reconstruction by a plastic surgeon. An interview study was conducted among 16 patients who had undergone surgical treatment by a dermatologist and reconstruction by a plastic surgeon for basal cell carcinoma, cutaneous squamous cell carcinoma, or lentigo maligna. The interviews focused on patients’ experiences and needs regarding care using a predefined topic list. All interviews were audio-taped, transcribed verbatim and inductively analyzed using Atlas.ti. Patients reported a need for a skilled and friendly physician who tailors information and communication to their individual situation. A need for continuity of care and improved collaboration between healthcare providers was also emphasized. Furthermore, patients experienced complications and unmet expectations and expressed a need for shared decision-making at various steps throughout the treatment process (depending on age). Patients also considered completeness of tumor removal, follow-up visits with multiple specialists to be planned the same day and recognition of the psychological impact of the disease on the partner important. To improve patient-centered care for complex skin cancer patients, more efforts should be directed towards improving continuity of care and collaboration. Furthermore, it is advocated for physicians to be sensitive to the individual needs of patients and their partner and adjust information, communication and (supportive) care accordingly

Substitution of low-risk skin cancer hospital care towards primary care: A qualitative study on views of general practitioners and dermatologists

Background Rising healthcare expenditures places the potential for substitution of hospital care towards primary care high on the political agenda. As low-risk basal cell carcinoma (BCC) care is one of the potential targets for substitution of hospital care towards primary care the objective of this study is to gain insight in the views of healthcare professionals regarding substitution of skin cancer care, and to identify perceived barriers and potential strategies to facilitate substitution. Methods A qualitative study was conducted consisting of 40 interviews with dermatologists and GPs and three focus groups with 18 selected GPs with noted willingness regarding substitution of skin cancer care. The interviews and focus groups focused on general views, perceived barriers and potential strategies to facilitate substitution of skin cancer care, using predefined topic lists. All sessions were audio-taped, transcribed verbatim and analyzed using the program AtlasTi. Results GPs were generally positive regarding substitution of skin care whereas dermatologists expressed more concerns. Lack of trust in GPs to adequately perform skin cancer care and a preference of patients for dermatologists are reported as barriers by dermatologists. The main barriers reported by GPs were a lack of confidence in own skills to perform skin cancer care, a lack of trust from both patients and dermatologists and limited time and financial compensation. Facilitating strategies suggested by both groups mainly focused on improving GPs’ education and improving the collaboration between primary and secondary care. GPs additionally suggested efforts from dermatologists to increase their own and patients’ trust in GPs, and time and financial compensation. The selected group of GPs suggested practical solutions to facilitate substitution focusing on changes in organizational structure including horizontal referring, outreach models and practice size reduction. Conclusions GPs and, to lesser extent, dermatologists are positive regarding substitution of low-risk BCC care, though report substantial barriers that need to be addressed before substitution can be further implemented. Aside from essential strategies such as improving GPs’ skin cancer education and time and financial compensation, rearranging the organizational structure in primary care and between primary and secondary care may facilitate effective and safe substitution of low-risk BCC care

From decision to reflection:understanding the experiences and unmet care needs of patients treated with immunotherapy for melanoma in the adjuvant or metastatic setting

BACKGROUND: Despite increased use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma, little is known about patient experiences during this treatment. This study aimed to gain an in-depth understanding of experiences and unmet care needs of patients treated in the adjuvant or metastatic setting for advanced melanoma regarding their ICI treatment trajectory.METHODS:Interviews and focus groups were conducted among 35 patients treated with ICIs in the adjuvant setting for completely resected stage III (n = 14), or in the metastatic setting for irresectable stage IV (n = 21) melanoma. A thorough thematic content analysis was conducted.RESULTS: Three main themes were identified. When (1) dealing with uncertainty in the decision-making process, adjuvant patients explored the pros and cons, whereas metastatic patients considered immunotherapy their only viable option. Both groups expressed the need for additional guidance. In (2) navigating the immunotherapy course, both perceived the trajectory as intense, experienced a major impact on their and their (close) relatives' lives, and felt the need to (re)gain control. When (3) looking back on the immunotherapy experience, metastatic patients generally felt relieved, while among adjuvant patients, feelings of doubt regarding their choice for ICIs were also reported.CONCLUSIONS: ICI treatment is perceived as intensive for both patient groups, facing both comparable and distinct challenges throughout the treatment trajectory, underscoring the need for stage-specific, individualised guidance. Options regarding flexible follow-ups, low-threshold contact and psychosocial support throughout the treatment trajectory should be explored.</p