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.

Impact of the COVID-19 pandemic on cancer care in Ireland - Perspectives from a COVID-19 and Cancer Working Group.

Upon the COVID-19 pandemic onset in Ireland, cancer service disruptions occurred due to prioritisation of COVID-19 related care, redeployment of staff, initial pausing of screening, diagnostic, medical and surgical oncology procedures, staff shortages due to COVID-19 infection and impacts on the physical and mental health of cancer healthcare workers. This was coupled with reluctance among people with symptoms suspicious for cancer to attend for clinical evaluation, due to concerns of contracting the virus. This was further compounded by a cyber-attack on national health service IT systems on May 14th 2021. The Irish Cancer Society, a national cancer charity with a role in advocacy, research and patient supports, convened a multi-disciplinary stakeholder group (COVID-19 and Cancer Working Group) to reflect on and understand the impact of the pandemic on cancer patients and services in Ireland, and discuss potential mitigation strategies. Perspectives on experiences were gathered across domains including timeliness of data acquisition and its conversion into intelligence, and the resourcing of cancer care to address cancer service impacts. The group highlighted aspects for future research to understand the long-term pandemic impact on cancer outcomes, while also highlighting potential strategies to support cancer services, build resilience and address delayed diagnosis. Additional measures include the need for cancer workforce recruitment and retention, increased mental health supports for both patients and oncology professionals, improvements to public health messaging, a near real-time multimodal national cancer database, and robust digital and physical infrastructure to mitigate impacts of the current pandemic and future challenges to cancer care systems.

Enduring psychological impact of childhood cancer on survivors and their families in Ireland: A national qualitative study.

OBJECTIVE: To establish the major expressed psychological needs of adult survivors of childhood cancer living in Ireland. METHODS: Seven focus groups were conducted with adult survivors of childhood cancer and their parents in 2018. Survivors were invited to participate if they were diagnosed with cancer before age 18. RESULTS: Thirty-three participants (15 survivors, 18 parents; 27 female, 6 male) were included. They had experienced a range of haematological and solid tumours. Five themes were generated: (a) Enduring psychological impact on survivors; many survivors experience delayed trauma and mental health crises in adulthood. (b) Enduring psychological impact on family members; parents and siblings have unmet psychological needs relating to the family's experience of cancer. (c) Enduring impact on family dynamics; survivors and parents expressed fear and guilt relating to cancer which impacted on family interactions. (d) Challenges accessing support; psychological support services are inadequate to meet expressed needs. (e) Desired model of care; no single service model appeals to all survivors, and flexibility is required in the delivery of psychological support. CONCLUSION: Adult survivors of childhood cancer and their family members experience enduring psychological effects relating to their diagnosis and treatment. Psychological support services are inadequate to meet the expressed needs of this growing population.

Aroma compound diacetyl suppresses glucagon-like peptide-1 production and secretion in STC-1 cells.

Diacetyl is a volatile flavour compound that has a characteristic buttery aroma and is widely used in the flavour industry. The aroma of a food plays an important role in food palatability and thus intake. This study investigates the effect of diacetyl on the satiety hormone, glucagon-like peptide (GLP-1), using the enteroendocrine cell line, STC-1. Diacetyl decreased proglucagon mRNA and total GLP-1 from glucose stimulated STC-1 cells. This dampening effect on GLP-1 appears to be mediated by increasing intracellular cAMP levels, increasing synthesis of the G protein coupled receptor, GPR120, and its recruitment to the cell surface. Voltage gated Ca2+ channels, K+ATP channels and the α-gustducin taste pathway do not appear to be involved. These findings demonstrate that components contributing to food palatability suppress GLP-1. This ability of diacetyl to reduce satiety signals may contribute to overconsumption of some palatable foods.

Ghrelin's Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction.

Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghrelin's orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghrelin's orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.