Melanoma-related costs by disease stage and phase of management in Ireland.

BACKGROUND: Management options for the treatment of melanoma have expanded in recent years. In an era of promising, but expensive novel pharmacological treatments, robust stage-specific melanoma-related cost estimates are necessary to support budgetary planning, evaluation of cost-effectiveness and to contribute to the investment case for prevention. METHODS: A detailed decision model, describing the melanoma care pathway (by disease stage) from diagnosis, through treatment and follow-up was developed over a 5-year time frame from the perspective of the Irish healthcare system. The model was populated with real-world data from the National Cancer Registry Ireland. Uncertainty was explored using one-way and probabilistic sensitivity analysis. RESULTS: The cost of managing a case of melanoma diagnosed at Stage IV (€122 985) was more than 25 times more expensive than managing a case diagnosed at Stage IA (€4269). Total costs were sensitive to the choice of immunotherapeutic and targeted drug, duration of treatment and proportion of patients receiving immunotherapy agents. CONCLUSIONS: The rising incidence of melanoma and high cost of new novel therapies presents an immediate challenge to cancer control and public health globally. This study highlights the cost differential between early and late detection and the potential return on investment for prevention versus high-cost treatment.

A flexural exanthem following postexposure prophylaxis.

We report a case of symmetrical drug-related intertriginous and flexural exanthema following antiretroviral postexposure prophylactic medications, tenofovir and emtricitabine, commencement of which preceded the onset of the rash. Tenofovir and emtricitabine are both nucleoside reverse transcriptase inhibitor medications, commonly used to prevent development of AIDS.

Smart allocation of restoration funds over space and time.

A challenge for natural area managers is to ensure that public expenditure on land restoration is cost effective, efficient and transparent but this is difficult to achieve in practice, especially when there are many possible projects across multiple years. Here we develop a "roadmap" for investment in land restoration. It explicitly considers space, time and their interaction, in relation to ecological outcomes and restoration costs (and their variation in time and space). Using integer linear programming optimization in a benefit-cost accounting framework, the roadmap incorporates: transitions between different stages of ecological recovery in a spatial mosaic of multiple ecosystem types; cost schedules associated with managing those transitions over time; time lags between beginning management and achieving outcomes; variations to constraints and goals associated with various factors including site accessibility, specific conservation priorities (such as threatened species or ecosystems); and background environmental trends. This approach enables land managers to: (1) forecast landscape-scale outcomes of management strategies over long timeframes; (2) address the question of how long it will take and how much it will cost to achieve specific outcomes; and (3) explore potential trade-offs in outcomes among alternative management strategies. We illustrate its application using a case study of forest restoration in Australia by a local government authority across a public conservation estate comprising 765 land units of varying size, totaling ˜13,000 ha, across five different floristic vegetation types, with an annual budget of ˜AU$5M, projected over a 50-yr timeframe. These simulations revealed a trade-off between management strategies that seek to increase either the total cover of native forest or the amount of high quality forest: quality-based strategies were favored in scenarios in which shorter term (20-30 yr) timeframes were chosen at the outset, but cover-based strategies were favored if longer time horizons were initially targeted. Projected outcomes were also strongly influenced by assumed background rates of vegetation decline or recovery. Many of the issues in this restoration roadmap are generalizable (even though specific outcomes and trade-offs are likely to vary among case studies), and the approach is both scalable and transferable to other regions and ecosystems.

Biological and JAK inhibitor therapy outcomes for severe psoriasis in trisomy 21.

Little is known about biological outcomes for severe psoriasis in trisomy 21 (T21). Our aim was to review outcomes of patients with T21 and severe psoriasis treated with biologic or Janus kinase inhibitors (JAKi). Information on demographics, co-morbidities, and therapeutic responses was retrospectively collated. Twenty-one patients were identified (mean age 24.7 years). Ninety percent (18/20) of TNFα inhibitor trials failed. Almost two-thirds (7/11) of patients achieved an adequate response with ustekinumab. All three patients treated with tofacitinib achieved an adequate response following at least three biologic failures. The mean number of biologic/JAKi therapies received was 2.1 with overall survival of 36%. Eighty-one percent (17/21) of patients required conversion from their index biologic treatment due to failure. In patients with T21 and severe psoriasis, failure of TNFα inhibition is common and ustekinumab therapy should be considered as first-line therapy. The role of JAKi is emerging.

Cutaneous Absidia corymbifera in a Lupus Nephritis Patient.

A 28-year-old farmer with class IV lupus nephritis presented with a two-week history of a right shin lesion. The lesion was purple in color, fungating, and indurated with a focus of deep ulceration at the inferior pole and punctate, bleeding from its surface. Three months earlier, he was started on induction immunosuppression for a relapse of his lupus nephritis. Since the diagnosis of lupus nephritis, nine years previously, he had had six flares of his disease and had been treated at different time points with cyclophosphamide, rituximab, and high-dose corticosteroids, without adverse events. Laboratory investigations showed improving kidney function (chronic kidney disease [CKD] stage IV) with reducing proteinuria, on his current immunosuppressive regimen. The differential diagnosis for this lesion was calciphylaxis, pyoderma gangrenosum, vasculitic lesion, or an infection. Histology and microbiological analysis confirmed the presence of Absidia corymbifera. He was treated with a combination of isavuconazole, reduction of his immunosuppressive agents, excision of the lesion, and skin grafting.

High Levels of Psychological Distress, Sleep Disturbance, and Alcohol Use Disorder in Adults With Atopic Dermatitis.

BACKGROUND: The burden of illness associated with atopic dermatitis (AD) is significant and multidimensional, especially in those with moderate to severe disease. OBJECTIVE: Our objective was to evaluate the disease burden of patients with AD in relation to psychological distress, sleep disturbance, and alcohol misuse. METHODS: Patients with AD, attending 2 tertiary referral centers in Dublin, Ireland, were recruited. A series of validated questionnaires were used including the Patient-Oriented Eczema Measure, Dermatology Life Quality Index (DLQI), Center for Epidemiologic Studies-Depression Scale, Quality of Life in Atopic Dermatitis Questionnaire, Alcohol Use Disorders Identification Test, and Pittsburgh Sleep Quality Index. The Eczema Area and Severity Index was calculated contemporaneously with the questionnaire completion. RESULTS: One hundred patients completed the questionnaire, of whom 52% were female. Sixty-three percent of patients experienced impaired quality of life as measured by the DLQI. Higher DLQI scores correlated with decreasing age (r = 0.3277, P < 0.0009). Thirty percent were found to be at risk of clinical depression, and higher Center for Epidemiologic Studies-Depression Scale scores correlated with a younger age and eczema severity. Sleep disturbance was greater in those at risk of depression (mean = 10.40 vs 5.79, P < 0.0001). Patients with moderate to severe AD were more likely to score higher on the Alcohol Use Disorders Identification Test, and 25% met the criteria for alcohol use disorder. In relation to sleep, 73% of patients scored higher than 5 on the Pittsburgh Sleep Quality Index, which signifies poor sleep quality. CONCLUSIONS: Patients with AD endure a significant burden on health with regard to mental well-being, alcohol use, and sleep quality. Clinicians should consider screening patients for these comorbidities.