Hyperglycaemia following immune checkpoint inhibitor therapy-Incidence, aetiology and assessment.

AIMS: We systematically studied the presence of hyperglycaemia during treatment with Immune Checkpoint Inhibitors (ICPI) for cancer, in those with and without diabetes at baseline, and determined the cause of new-onset hyperglycaemia, METHODS: Retrospective review of electronic records of those receiving an ICPI for melanoma, lung or renal cancer. RESULTS: Overall, 959 participants were included. In this study, 103 had diabetes at baseline (10.7%). Those with lung cancer had the highest frequency of diabetes; 131 people had hyperglycaemia (defined as at least one glucose ≥11.1 mmol/L) in the year after starting an ICPI. The incidence was 55% in those with diabetes at baseline, and 8.6% in those without baseline diabetes. Among 74 with new-onset hyperglycaemia (without pre-existing diabetes) 76% was attributable to steroid induced diabetes, with 9.5% due to ICPI Induced diabetes resembling type 1 diabetes. CONCLUSIONS: Hyperglycaemia is common in persons receiving an ICPI for cancer, including 8.6% of those without known diabetes. While much of this is due to glucocorticoid use, care is needed to avoid missing those with ICPI-induced diabetes who are at risk of diabetic ketoacidosis, which is a medical emergency.

What is the impact of multimorbidity on out-of-pocket healthcare expenditure among community-dwelling older adults in Ireland? A cross-sectional study.

OBJECTIVES: Individuals with multimorbidity use more health services and take more medicines. This can lead to high out-of-pocket (OOP) healthcare expenditure. This study, therefore, aimed to assess the association between multimorbidity (two or more chronic conditions) and OOP healthcare expenditure in a nationally representative sample of adults aged 50 years or over. DESIGN: Cross-sectional analysis of data collected in 2016 from wave 4 of The Irish Longitudinal Study on Ageing.SettingIreland.ParticipantsCommunity-dwelling adults aged 50 years and over.MethodA generalised linear model with log-link and gamma distributed errors was fitted to assess the association between multimorbidity and OOP healthcare expenditure (including general practitioner, emergency department, outpatients, specialist consultations, hospital admissions, home care and prescription drugs). RESULTS: Overall, 3453 (58.5%) participants had multimorbidity. Among those with any OOP healthcare expenditure, individuals with multimorbidity spent more on average per annum (€806.8 for two conditions, €885.8 for three or more conditions), than individuals with no conditions (€580.3). Pharmacy-dispensed medicine expenditure was the largest component of expenditure. People with multimorbidity on average spent more of their equivalised household income on healthcare (7.1% for two conditions, 9.7% for three or more conditions), than people with no conditions (5.0%). A strong positive association was found between number of conditions and OOP healthcare expenditure (p<0.001) and between having private health insurance and OOP healthcare expenditure (p<0.001). A strong negative association was found between eligibility for free primary/hospital care and heavily subsidised medicines and OOP healthcare expenditure (p<0.001). CONCLUSIONS: This study suggests that having multimorbidity in Ireland increases OOP healthcare expenditure, which is problematic for those with more conditions who have lower incomes. This highlights the need for this financial burden to be considered when designing healthcare/funding systems to address multimorbidity, so that access to essential healthcare can be maximised for those with greatest need.

Variation of prescription drug prices in community pharmacies: A national cross-sectional study.

Background; There is evidence of significant variation of prescription drug prices in community pharmacies in several countries. Prescription drugs are a major source of expenditure for patients. High prices can lead to cost-related non-adherence and adverse health outcomes. Objective; This study's aim was to establish the variation and availability of prescription drug prices in community pharmacies in Ireland. Methods; Using a cross-sectional design, prices were sought in community pharmacies using phone, email and website enquiries. A purposive sample of 12 prescription drugs was included. The prescription drugs were selected from the top 100 medications by dispensing frequency in 2017 on Ireland's main state drug scheme. For each pharmacy, the price was checked for three drugs only. Researchers sought to contact 1,500 pharmacies by phone and 320 by email, as well as consult the website of 370 pharmacies. Results; In total, 1,529 pharmacies responded to queries, 1,362 by telephone and 167 by email. Overall, 88.5% (N = 1,353) of pharmacies who answered queries, provided prices. For each drug, the average price quoted to researchers was higher than the price paid by the state for patients who can access subsidised medicines. The ratio of 90th to 10th percentile prices ranged from 1.3 to 2.0 for the twelve drugs. A Welch's t-test found that for nine of the 12 drugs, the price was significantly higher (p < .05) for chain pharmacies compared to independent pharmacies. Conclusions; Evidence was found of significant price variation in community pharmacies. There was also evidence that some community pharmacies were not following regulatory guidance on drug pricing transparency. Policy measures such as mandated price transparency, or fixed prescription drug prices could help address these price issues.

GPs' perceptions of their relationship with the pharmaceutical industry: a qualitative study.

BACKGROUND: The pharmaceutical industry invests heavily in promoting medications to physicians. This promotion may influence physicians' prescribing behaviour and lead to inappropriately increased prescribing rates. AIM: To understand GPs' experience of interacting with the pharmaceutical industry, and explore their views and perceptions of the impact of this interaction in general practice in Ireland. DESIGN & SETTING: A qualitative design was used, and GPs practicing in Ireland were eligible. METHOD: A combination of purposive and snowball sampling techniques was applied and semi-structured interviews were conducted. Thematic analysis was used to develop themes from the data. RESULTS: Twenty-one GPs and one GP trainee participated. Five themes were developed: 1) GP and pharmaceutical industry interface; 2) the industry's methods of influence; 3) the uncomfortable relationship between GPs and industry; 4) GPs' perceptions of being unconsciously influenced; and 5) GPs' lack of knowledge of relevant regulations.Participants interacted with pharmaceutical representatives in their surgery and through continuing professional development (CPD). Reported methods of influence included biased information and the offer of gifts. Most participants felt their prescribing was unconsciously influenced. A minority felt that they were only influenced in a way that improved their prescribing. CONCLUSION: The study shows that there can be a lack of clarity among GPs about relevant regulations and about the potential impact on prescribing of interactions with the pharmaceutical industry. Education of trainees and GPs has the potential to address this. Restrictions on interactions with the pharmaceutical industry may also play a role, although alternative CPD funding sources would need to be established.

Payments reported by the pharmaceutical industry in Ireland from 2015 to 2019: An observational study.

BACKGROUND: The pharmaceutical industry makes large numbers of payments to healthcare organisations (HCOs) and healthcare professionals (HCPs). Ireland has a large pharmaceutical industry presence and national debate on legislating for greater industry payment transparency. This study characterises payments in Ireland to HCPs and HCOs during 2015-2019, and the content, consistency and methodology of the data source. METHODS: An observational study of TransfersOfValue.ie, the disclosure website for the Irish Pharmaceutical Health Association pharmaceutical companies. We conducted a quantitative analysis, summarising payments to HCOs, HCPs and for research and development (R&D). We quantified disclosure rates of names for HCP and HCO payment recipients. We also conducted a content analysis of the methodology notes and website content. RESULTS: Payments totalling €163 million were reported by 47 companies during 2015-2019, €84.6 million for R&D, with non-R&D payments of €45.1 million to HCOs and €33.6 million to HCPs. HCOs were named for 91.2% of payments, and HCPs for 55.1-62.8% across study years. For 2019, ten companies disclosed >€1 million in payments, and three disclosed >€1 million in HCO and HCP payments. Content analysis of 132 data reports and 46 methodology notes indicated substantial variation in methodologies for reporting between companies. CONCLUSIONS: There are substantial payments in Ireland, often the recipient is undisclosed, and companies differ in their reporting. A mandatory disclosure system could enhance transparency.

The experience of financial burden for people with multimorbidity: A systematic review of qualitative research.

BACKGROUND: Multimorbidity prevalence is increasing globally. People with multimorbidity have higher health care costs, which can create a financial burden. OBJECTIVE: To synthesize qualitative research exploring experience of financial burden for people with multimorbidity. SEARCH STRATEGY: Six databases were searched in May 2019. A grey literature search and backward and forward citation checking were also conducted. INCLUSION CRITERIA: Studies were included if they used a qualitative design, conducted primary data collection, included references to financial burden and had at least one community-dwelling adult participant with two or more chronic conditions. DATA EXTRACTION AND SYNTHESIS: Screening and critical appraisal were conducted by two reviewers independently. One reviewer extracted data from the results section; this was checked by a second reviewer. GRADE-CERQual was used to summarize the certainty of the evidence. Data were analysed using thematic synthesis. MAIN RESULTS: Forty-six studies from six continents were included. Four themes were generated: the high costs people with multimorbidity experience, the coping strategies they use to manage these costs, and the negative effect of both these on their well-being. Health insurance and government supports determine the manageability and level of costs experienced. DISCUSSION: Financial burden has a negative effect on people with multimorbidity. Continuity of care and an awareness of the impact of financial burden of multimorbidity amongst policymakers and health care providers may partially address the issue. PATIENT OR PUBLIC CONTRIBUTION: Results were presented to a panel of people with multimorbidity to check whether the language and themes 'resonated' with their experiences.

The experience of financial burden for patients with multimorbidity: A protocol for a systematic review of qualitative research.

Introduction: Multimorbidity is increasingly important due to its high disease burden, prevalence and related high healthcare utilisation. For patients, there is also a high financial burden due to direct and indirect costs arising from their multimorbidity. It is unclear how this financial burden affects patients. This study aims to synthesise qualitative evidence exploring the experience of financial burden from the perspective of patients with multimorbidity. Methods: The review will be reported using the ENTREQ guidelines. A systematic search of Lilacs, PubMed, CINAHL, EMBASE, PsycINFO, and Applied Social Sciences Index and Abstracts will be conducted using a predefined search strategy. A search of fourteen pre-specified websites will be conducted for grey literature. Forward and backward citation checking of included studies will be conducted also. Studies will be included if they contain primary qualitative research and reference the experience of financial burden from the perspective of adult (≥ 18 years) community dwelling patients with multimorbidity. Studies from any country and in any language will be included. Titles and abstracts of search results will be screened; if a study appears relevant, then full-texts will be screened for eligibility. Study characteristics of included articles will be extracted. Study quality will be evaluated using the critical appraisal skills programme (CASP) checklist for qualitative research. These three processes will be carried out by two reviewers independently. Thematic-synthesis will be used to analyse data. This will be carried out by one reviewer and cross-checked by a second reviewer. The GRADE CERQual approach will be used to assess the overall confidence in the evidence. Discussion: This review will identify evidence on the experiences of financial burden for patients with multimorbidity and forms part of a project to support consideration of financial burden for patients in the development of clinical guidelines in Ireland. PROSPERO registration number: CRD42019135284.

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma.

BACKGROUND: The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations. METHODS: Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance. RESULTS: The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models. CONCLUSIONS: An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care.

The cost of ipilimumab toxicity: a single-centre analysis.

There are no published data on the costs associated with investigating and managing toxicity from ipilimumab treatment in patients with metastatic melanoma. Patients treated with ipilimumab at The Royal Marsden Hospital between 1 September 2010 and 1 April 2013 were identified. Data on demographics, investigations and survival outcomes were collected. Patients with grade 3 or higher immune-related adverse events were identified, and costs of investigating and managing toxicities in them were calculated on the basis of standard National Health Service tariffs. Out of the 110 patients, 29 experienced grade 3/4 immune-related adverse events. The total cost of investigating and managing these patients was £140,680, or a median cost of £2860 per patient. Patients experiencing grade 3/4 toxicities had 1-, 2- and 3-year survival rates of 79, 59 and 46%, compared with 24, 17 and 15% in the group that did not experience significant toxicity (P<0.0005). The most common treatment-related toxicity identified was colitis. Two patients died from complications associated with ipilimumab colitis. The cost of ipilimumab toxicity is marginal in comparison with the total treatment cost. Patients treated with ipilimumab who develop significant toxicity have a higher than expected 1-, 2- and 3-year survival.

Preliminary clinical assessment of the relationship between tumor alphavbeta3 integrin and perfusion in patients studied with [(18)F]fluciclatide kinetics and [ (15)O]H 2O PET.

BACKGROUND: [(18)F]fluciclatide, a peptide ligand with high affinity for αvß3/αvß5 integrins, is a proposed biomarker of tumor angiogenesis. The study rationale was to perform a preliminary evaluation of the relationship between tumor [(18)F]fluciclatide uptake and perfusion by [(15)O]H2O PET. METHODS: Patients with non-small cell lung cancer and melanoma underwent dynamic imaging with arterial sampling following injection of [(15)O]H2O and [(18)F]fluciclatide. Quantification was performed using a one-tissue compartmental model for [(15)O]H2O and a two-tissue model for [(18)F]fluciclatide at volume-of-interest level, and SUV at voxel level. RESULTS: Tumor binding potential (k 3/k 4 ratio) of [(18)F]fluciclatide tumor was 5.39 ± 1.46, consistent with previous studies in breast cancer metastases. Voxel-by-voxel maps of [(18)F]fluciclatide delivery strongly correlated with [(15)O]H2O-based perfusion (p < 10(-4) tumor, 1,794 ± 1,331 voxels). Interestingly, this correlation was lost when retention of [(18)F]fluciclatide at late time-points was compared with perfusion (p > 0.15). CONCLUSIONS: Our study suggests tumor [(18)F]fluciclatide retention is unrelated to tumor perfusion, supporting use of late (60-min) imaging protocols in patients.