Concurrent Varicella-Zoster Virus Reactivation and Recurrent Herpes Simplex Virus Infection in the C2 Dermatome With Varicella-Zoster Virus Encephalitis: A Case Report and Review of the Literature.

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are common viruses that are present in the general population. However, it is uncommon for both viruses to coincide at the same time and location. These viruses infect the nervous system to establish latency and have been associated with neurological disorders. We discuss a case of co-occurring VZV reactivation and recurrent HSV infection with subsequent VZV encephalitis following an insult to the neurologic system.

Structural insights into CXCR4 modulation and oligomerization.

Activation of the chemokine receptor CXCR4 by its chemokine ligand CXCL12 regulates diverse cellular processes. Previously reported crystal structures of CXCR4 revealed the architecture of an inactive, homodimeric receptor. However, many structural aspects of CXCR4 remain poorly understood. Here, we use cryo-electron microscopy to investigate various modes of human CXCR4 regulation. CXCL12 activates CXCR4 by inserting its N terminus deep into the CXCR4 orthosteric pocket. The binding of US Food and Drug Administration-approved antagonist AMD3100 is stabilized by electrostatic interactions with acidic residues in the seven-transmembrane-helix bundle. A potent antibody blocker, REGN7663, binds across the extracellular face of CXCR4 and inserts its complementarity-determining region H3 loop into the orthosteric pocket. Trimeric and tetrameric structures of CXCR4 reveal modes of G-protein-coupled receptor oligomerization. We show that CXCR4 adopts distinct subunit conformations in trimeric and tetrameric assemblies, highlighting how oligomerization could allosterically regulate chemokine receptor function.

Agonist antibody to guanylate cyclase receptor NPR1 regulates vascular tone.

Heart failure is a leading cause of morbidity and mortality1,2. Elevated intracardiac pressures and myocyte stretch in heart failure trigger the release of counter-regulatory natriuretic peptides, which act through their receptor (NPR1) to affect vasodilation, diuresis and natriuresis, lowering venous pressures and relieving venous congestion3-8. Recombinant natriuretic peptide infusions were developed to treat heart failure but have been limited by a short duration of effect9,10. Here we report that in a human genetic analysis of over 700,000 individuals, lifelong exposure to coding variants of the NPR1 gene is associated with changes in blood pressure and risk of heart failure. We describe the development of REGN5381, an investigational monoclonal agonist antibody that targets the membrane-bound guanylate cyclase receptor NPR1. REGN5381, an allosteric agonist of NPR1, induces an active-like receptor conformation that results in haemodynamic effects preferentially on venous vasculature, including reductions in systolic blood pressure and venous pressure in animal models. In healthy human volunteers, REGN5381 produced the expected haemodynamic effects, reflecting reductions in venous pressures, without obvious changes in diuresis and natriuresis. These data support the development of REGN5381 for long-lasting and selective lowering of venous pressures that drive symptomatology in patients with heart failure.

Internal Psychometric Validation of an International Burden of Illness Survey for Idiopathic Multicentric Castleman Disease.

INTRODUCTION: Idiopathic multicentric Castleman disease (iMCD) is a rare, chronic, debilitating lymphoproliferative disorder where the mainstay of treatment is symptom management. Our recent international patient survey showed that patients with iMCD have a high symptom burden that has a significant negative patient-reported impact on several aspects of daily life. As part of our ongoing work towards the development of an iMCD symptom burden scale, assessing the survey's psychometric properties is a critical step in understanding its adequacy, relevance, and usefulness. As iMCD is a rare disease, there are challenges to conducting such psychometric analyses which we describe. METHODS: As part of the exploratory psychometric analysis, three a priori hypothesis sets (HS) were generated by interviewing an iMCD-experienced clinician, a patient, and a caregiver to explore the iMCD patient survey's internal construct validity, given no gold standard iMCD measure exists for external construct validation. HS-1 hypothesized that a convergent or discriminant relationship exists with the patients' self-assessment of symptom effect on daily life between two potentially related or unrelated symptoms, respectively. HS-2 hypothesized that having a greater number of symptoms has a positive convergent relationship with the patients' assessment of symptoms' effect on daily life. Finally, HS-3 hypothesized that patients receiving treatment versus no treatment was associated with patients reporting less effect of symptom burden on their daily life. Spearman's rank absolute correlation strength (ACS) was used for HS-1 and HS-2 (convergent relationship, ACS ≥ 0.3 and p value < 0.05; divergent relationship, ACS < 0.3), and Cohen's d to quantify standardized absolute effect sizes (AES) for HS-3 (AES ≥ 0.5 and p value < 0.05). RESULTS: Our analyses partially supported HS-1. None of the three positive convergent relationships were supported. Of the six discriminant relationships, only dizziness with impaired cognitive function and tiredness with dizziness were supported. HS-2 analyses showed there was convergent validity between the number of symptoms and their effect on aspects of daily life. HS-3 analyses did not provide evidence to support the hypothesis. CONCLUSION: These internal psychometric construct analyses provide initial support for the bespoke iMCD patient survey and will guide additional work towards the development of the first iMCD-specific symptom burden scale.

Direct and Indirect Costs of Breast Cancer and Associated Implications: A Systematic Review.

INTRODUCTION: Breast cancer is currently the leading cause of global cancer incidence. Breast cancer has negative consequences for society and economies internationally due to the high burden of disease which includes adverse epidemiological and economic implications. Our aim is to systematically review the estimated economic burden of breast cancer in the United States (US), Canada, Australia, and Western Europe (United Kingdom, France, Germany, Spain, Italy, Norway, Sweden, Denmark, Netherlands, and Switzerland), with an objective of discussing the policy and practice implications of our results. METHODS: We included English-language published studies with cost as a focal point using a primary data source to inform resource usage of women with breast cancer. We focussed on studies published since 2017, but with reported costs since 2012. A systematic search conducted on 25 January 2023 identified studies relating to the economic burden of breast cancer in the countries of interest. MEDLINE, Embase, and EconLit databases were searched via Ovid. Study quality was assessed based on three aspects: (1) validity of cost findings; (2) completeness of direct cost findings; and (3) completeness of indirect cost findings. We grouped costs based on country, cancer stage (early compared to metastatic), and four resource categories: healthcare/medical, pharmaceutical drugs, diagnosis, and indirect costs. Costs were standardized to the year 2022 in US (US$2022) and International (Int$2022) dollars. RESULTS: Fifty-three studies were included. Studies in the US (n = 19) and Canada (n = 9) were the majority (53%), followed by Western European countries (42%). Healthcare/medical costs were the focus for the majority (89%), followed by pharmaceutical drugs (25%), then diagnosis (17%) and indirect (17%) costs. Thirty-six (68%) included early-stage cancer costs, 17 (32%) included metastatic cancer costs, with 23% reporting costs across these cancer stages. No identified study explicitly compared costs across countries. Across cost categories, cost ranges tended to be higher in the US than any other country. Metastatic breast cancer was associated with higher costs than earlier-stage cancer. When indirect costs were accounted for, particularly in terms of productivity loss, they tended to be higher than any other estimated direct cost (e.g., diagnosis, drug, and other medical costs). CONCLUSION: There was substantial heterogeneity both within and across countries for the identified studies' designs and estimated costs. Despite this, current empirical literature suggests that costs associated with early initiation of treatment could be offset against potentially avoiding or reducing the overall economic burden of later-stage and more severe breast cancer. Larger scale, national, economic burden studies are needed, to be updated regularly to ensure there is an ongoing and evolving perspective of the economic burden of conditions such as breast cancer to inform policy and practice.

Mapping functions for the PHQ-9 and GAD-7 to generate EQ-5D-3L for economic evaluation.

PURPOSE: Generic preferenced-based measures, such as EQ-5D-3L, that are used to estimate quality adjusted life years (QALYs) for economic evaluation are not always available in clinical trials. Predicting EQ-5D-3L values from the commonly used Patient Health Questionnaire 9 (PHQ-9) and Generalised Anxiety Disorder-7 (GAD-7) would allow estimation of QALYs from such trials. The aim was to provide mapping functions to estimate EQ-5D-3L from PHQ-9 and GAD-7 to facilitate economic evaluation. METHODS: Data was drawn from four trials of patients with symptoms of depression testing collaborative care or computerised cognitive behavioural therapy. Patients completed PHQ-9, GAD-7, and EQ-5D-3L at different timepoints. Mapping was undertaken using adjusted limited dependent variable mixture models (ALDVMM), ordinary least squares (OLS), and Tobit models based on PHQ-9, GAD-7 scores or questions, and age to predict EQ-5D-3L utilities. Models were selected based on mean error (ME), mean absolute error (MAE), root mean squared error (RMSE), model goodness of fit, and visual inspection of the predictions. RESULTS: There were 5583 and 3942 observations for EQ-5D-3L combined with PHQ-9 and GAD-7 respectively. ALDVMM models had low ME ( ≤|0.0018|) and MAE ranging from 0.189 to 0.192, while RMSE was from 0.251 to 0.254 and had better predictions than OLS and Tobit models. ALDVMM models with four components based on PHQ-9 and GAD-7 scores are recommended for estimating EQ-5D-3L utilities. CONCLUSIONS: Recommended mapping functions provide users with an approach to estimate EQ-5D-3L utilities for economic evaluation using PHQ-9, GAD-7, or both scores where they have been used together.

Is Economic Evaluation and Care Commissioning Focused on Achieving the Same Outcomes? Resource-Allocation Considerations and Challenges Using England as a Case Study.

Commissioning describes the process of contracting appropriate care services to address pre-identified needs through pre-agreed payment structures. Outcomes-based commissioning (i.e., paying services for pre-agreed outcomes) shares a common goal with economic evaluation: achieving value for money for relevant outcomes (e.g., health) achieved from a finite budget. We describe considerations and challenges as to the practical role of relevant outcomes for evaluation and commissioning, seeking to bridge a gap between economic evaluation evidence and care commissioning. We describe conceptual (e.g., what are 'relevant' outcomes) alongside practical considerations (e.g., quantifying and using relevant endpoint or surrogate outcomes) and pertinent issues when linking outcomes to commissioning-based payment mechanisms, using England as a case study. Economic evaluation often focuses on a single endpoint health-focused maximand, e.g., quality-adjusted life-years (QALYs), whereas commissioning often focuses on activity-based surrogate outcomes (e.g., health monitoring), as easier-to-measure key performance indicators that are more acceptable (e.g., by clinicians) and amenable to being linked with payment structures. However, payments linked to endpoint and/or surrogate outcomes can lead to market inefficiencies; for example, when surrogates do not have the intended causal effect on endpoint outcomes or when service activity focuses on only people who can achieve prespecified payment-linked outcomes. Accounting for and explaining direct links from commissioners' payment structures to surrogate and then endpoint economic outcomes is a vital step to bridging a gap between economic evaluation approaches and commissioning. Decision-analytic models could aid this but they must be designed to account for relevant surrogate and endpoint outcomes, the payments assigned to such outcomes, and their interaction with the system commissioners purport to influence.

Estimating the effectiveness of an enhanced 'Improving Access to Psychological Therapies' (IAPT) service addressing the wider determinants of mental health: a real-world evaluation.

BACKGROUND: Addressing the wider determinants of mental health alongside psychological therapy could improve mental health service outcomes and population mental health. OBJECTIVES: To estimate the effectiveness of an enhanced 'Improving Access to Psychological Therapies' (IAPT) mental health service compared with traditional IAPT in England. Alongside traditional therapy treatment, the enhanced service included well-being support and community service links. DESIGN: A real-world evaluation using IAPT's electronic health records. SETTING: Three National Health Service IAPT services in England. PARTICIPANTS: Data from 17 642 service users classified as having a case of depression and/or anxiety at baseline. INTERVENTION: We compared the enhanced IAPT service (intervention) to an IAPT service in a different region providing traditional treatment only (geographical control), and the IAPT service with traditional treatment before additional support was introduced (historical control). PRIMARY OUTCOME MEASURES: Patient Health Questionnaire-9 (PHQ-9) Depression Scale (score range: 0-27) and Generalised Anxiety Disorder-7 (GAD-7) Anxiety Scale (score range: 0-21); for both, lower scores indicate better mental health. Propensity scores were used to estimate inverse probability of treatment weights, subsequently used in mixed effects regression models. RESULTS: Small improvements (mean, 95% CI) were observed for PHQ-9 (depression) (-0.21 to -0.32 to -0.09) and GAD-7 (anxiety) (-0.23 to -0.34 to -0.13) scores in the intervention group compared with the historical control. There was little evidence of statistically significant differences between intervention control and geographical control. CONCLUSIONS: Embedding additional health and well-being (H&W) support into standard IAPT services may lead to improved mental health outcomes. However, the lack of improved outcomes compared with the geographical control may instead reflect a more general improvement to the intervention IAPT service. It is not clear from our findings whether an IAPT service with additional H&W support is clinically superior to traditional IAPT models.

Navigating data governance associated with real-world data for public benefit: an overview in the UK and future considerations.

Real-world data encompass data primarily captured for the provision or operation of services, for example, electronic health records for direct care purposes, but which may have secondary uses for informing research or commissioning. Public benefit is potentially forfeited by the underutilisation of real-world data for secondary uses, in part due to risk aversion when faced with the prospect of navigating necessary and important data governance processes. Such processes can be perceived as complex, daunting, time-consuming and exposing organisations to risk. By providing an overview description and discussion around the role of six key legal and information governance frameworks and their role regarding responsible data access, linkage and sharing, our intention is to make data governance a less daunting prospect and reduce the perception that it is a barrier to secondary uses, thus enabling public benefit.

Covariates of success in quitting smoking: a systematic review of studies from 2008 to 2021 conducted to inform the statistical analyses of quitting outcomes of a hospital-based tobacco dependence treatment service in the United Kingdom.

Background: Smoking cessation interventions are being introduced into routine secondary care in the United Kingdom (UK), but there are person and setting-related factors that could moderate their success in quitting smoking. This review was conducted as part of an evaluation of the QUIT hospital-based tobacco dependence treatment service ( https://sybics-quit.co.uk). The aim of the review was to identify a comprehensive set of variables associated with quitting success among tobacco smokers contacting secondary healthcare services in the UK who are offered support to quit smoking and subsequently set a quit date. The results would then be used to inform the development of a statistical analysis plan to investigate quitting outcomes. Methods: Systematic literature review of five electronic databases. Studies eligible for inclusion investigated quitting success in one of three contexts: (a) the general population in the UK; (b) people with a mental health condition; (c) quit attempts initiated within a secondary care setting. The outcome measures were parameters from statistical analysis showing the effects of covariates on quitting success with a statistically significant (i.e., p-value <0.05) association. Results: The review identified 29 relevant studies and 14 covariates of quitting success, which we grouped into four categories: demographics (age; sex; ethnicity; socio-economic conditions; relationship status, cohabitation and social network), individual health status and healthcare setting (physical health, mental health), tobacco smoking variables (current tobacco consumption, smoking history, nicotine dependence; motivation to quit; quitting history), and intervention characteristics (reduction in amount smoked prior to quitting, the nature of behavioural support, tobacco dependence treatment duration, pharmacological aids). Conclusions: In total, 14 data fields were identified that should be considered for inclusion in datasets and statistical analysis plans for evaluating the quitting outcomes of smoking cessation interventions initiated in secondary care contexts in the UK. PROSPERO registration: CRD42021254551 (13/05/2021).

Stop smoking interventions are being incorporated as a systematic and opt-out component of secondary care services in the UK's National Health Service (NHS), driven by the NHS's Long Term Plan. This review was conducted as part of an evaluation of the QUIT hospital-based tobacco dependence treatment service ( https://sybics-quit.co.uk). To support the development of statistical analyses to find out what affects smokers' success in quitting smoking after contacting the service, research was needed to identify what characteristics of the individual smokers and the healthcare setting might be important for success in quitting. The main purpose of the review was to support the development of a statistical analysis plan of quitting outcomes. We looked at academic papers published between 2008 and 2021 that estimated the influence of different factors on success in quitting smoking. The results of the review summarise the list of factors that previous studies have found to have an influence on quitting outcomes. The list of factors was used to inform discussions with the service about what data fields it would be important for the service to collect because that data could be important for helping the service to understand variation in quitting outcomes.

Symptom burden in patients with idiopathic multicentric Castleman disease and its impact on daily life: an international patient and caregiver survey.

Background: Idiopathic Multicentric Castleman Disease (iMCD) is a rare inflammatory lymphoproliferative disorder with heterogenous clinical presentations. The symptomatology in iMCD patients remains poorly understood. The aim of this study was to identify the type, frequency and severity of iMCD-related symptoms and the impact of these on the daily lives of iMCD patients and informal-caregivers. Methods: We conducted two bespoke 45-question online surveys for iMCD patients and informal-caregivers of patients recruited from the US, UK, Australia and Canada between April 14 and November 8, 2021. Descriptive data was collected, and a Likert scale was used to quantify the impact of symptoms on various aspects of daily life. Ordinal logistic regression analysis was used to determine associations between age, gender, employment status and symptom burden with aspects of daily life. Findings: Eligible respondents included 51 iMCD patients and 11 informal-caregivers. Patients reported up to 27 unique symptoms, the mean number of symptoms experienced by a patient was 6.7 (range 0-22 symptoms). Most symptoms had a moderate to severe impact on patients' daily lives, with 'pain/discomfort', 'ability to travel', and 'sexual functioning' being the most impacted. iMCD patient characteristics such as being 40 years or older, female, and either disabled or unemployed was significantly associated with adverse impact on several aspects of daily life. Among caregivers, the aspects of daily life that were disproportionately affected was their own social life and freedom, emotional wellbeing, travel/relocation, and work. Interpretation: iMCD patients have widely varied and unappreciated symptomatology. High symptom burden adversely impacts several aspects of patient daily lives as well as their caregivers. Funding: Funding was provided by EUSA Pharma.

Enabling QALY estimation in mental health trials and care settings: mapping from the PHQ-9 and GAD-7 to the ReQoL-UI or EQ-5D-5L using mixture models.

PURPOSE: Patient-reported outcome measures (PROMs) are commonly collected in trials and some care settings, but preference-based PROMs required for economic evaluation are often missing. For these situations, mapping models are needed to predict preference-based (aka utility) scores. Our objective is to develop a series of mapping models to predict preference-based scores from two mental health PROMs: Patient Health Questionnaire-9 (PHQ-9; depression) and Generalised Anxiety Questionnaire-7 (GAD-7; anxiety). We focus on preference-based scores for the more physical-health-focussed EQ-5D (five-level England and US value set, and three-level UK cross-walk) and more mental-health-focussed Recovering Quality-of-Life Utility Index (ReQoL-UI). METHODS: We used trial data from the Improving Access to Psychological Therapies (IAPT) mental health services (now called NHS Talking Therapies), England, with a focus on people with depression and/or anxiety caseness. We estimated adjusted limited dependent variable or beta mixture models (ALDVMMs or Betamix, respectively) using GAD-7, PHQ-9, age, and sex as covariates. We followed ISPOR mapping guidance, including assessing model fit using statistical and graphical techniques. RESULTS: Over six data collection time-points between baseline and 12-months, 1340 observed values (N ≤ 353) were available for analysis. The best fitting ALDVMMs had 4-components with covariates of PHQ-9, GAD-7, sex, and age; age was not a probability variable for the final ReQoL-UI mapping model. Betamix had practical benefits over ALDVMMs only when mapping to the US value set. CONCLUSION: Our mapping functions can predict EQ-5D-5L or ReQoL-UI related utility scores for QALY estimation as a function of variables routinely collected within mental health services or trials, such as the PHQ-9 and/or GAD-7.

VSIG4 interaction with heparan sulfates inhibits VSIG4-complement binding.

V-set and immunoglobulin domain-containing 4 (VSIG4) is a complement receptor of the immunoglobulin superfamily that is specifically expressed on tissue resident macrophages, and its many reported functions and binding partners suggest a complex role in immune function. VSIG4 is reported to have a role in immune surveillance as well as in modulating diverse disease phenotypes such as infections, autoimmune conditions, and cancer. However, the mechanism(s) governing VSIG4's complex, context-dependent role in immune regulation remains elusive. Here, we identify cell surface and soluble glycosaminoglycans, specifically heparan sulfates, as novel binding partners of VSIG4. We demonstrate that genetic deletion of heparan sulfate synthesis enzymes or cleavage of cell-surface heparan sulfates reduced VSIG4 binding to the cell surface. Furthermore, binding studies demonstrate that VSIG4 interacts directly with heparan sulfates, with a preference for highly sulfated moieties and longer glycosaminoglycan chains. To assess the impact on VSIG4 biology, we show that heparan sulfates compete with known VSIG4 binding partners C3b and iC3b. Furthermore, mutagenesis studies indicate that this competition occurs through overlapping binding epitopes for heparan sulfates and complement on VSIG4. Together these data suggest a novel role for heparan sulfates in VSIG4-dependent immune modulation.

Perspectives on an enhanced 'Improving Access to Psychological Therapies' (IAPT) service addressing the wider determinants of mental health: a qualitative study.

BACKGROUND: A new Health and Wellbeing pathway was introduced into the Improving Access to Psychological Therapies (IAPT) service in one geographical area of the UK in 2021 to address the wider determinants of mental health problems. It comprised assisted signposting to wider services and physical health promotion. This qualitative study aimed to understand stakeholders' experiences of implementing and receiving this new support and the barriers and facilitators to its delivery. METHODS: Forty-seven interviews were conducted, with service developers (n = 6), service deliverers (n = 12), service users (n = 22) and community and clinical partners (n = 7), as part of a larger mixed-methods evaluation. Interviews were recorded, transcribed, and analysed using reflexive thematic analysis. RESULTS: Three themes spanned all participant groups and represented key aspects of the service: (1) identifying suitability, (2) a holistic service, and (3) moving forward. The sub-themes represent the barriers and facilitators to processes working in practice, lending insight into potential service improvements. These included strengthening the quality of communication during referral and assessment, tailoring the support and delivery mode, and increasing transparency around continued care to drive sustained benefits. LIMITATIONS: Service users may have been selected due to their positive experiences of IAPT and were not demographically representative of the population, although participants' experiences of the service did suggest variation in our sample. CONCLUSIONS: The Health and Wellbeing pathway was perceived as having a positive impact on mental health and could reduce the burden on therapeutic services. However, service- and individual-level barriers need to be addressed to enhance statutory and community support links, manage service users' expectations, and improve accessibility for certain groups.

Pseudoxanthoma-elasticum-like changes on the soft palate.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive genetic disorder characterized by aberrant fragmentation and calcification of elastic fibers, leading to characteristic cutaneous, ophthalmic, and cardiovascular manifestations. PXE demonstrates significant phenotypic variability; involvement of the oral mucosa may be the only clue to the diagnosis. Reports on mucous membrane involvement in PXE are scarce. Here, we present a case of PXE-like changes in the oral cavity. A 70-year-old male patient presented with a painless leukoplakic lesion on the soft palate. Biopsy revealed numerous degenerated fibers in the lamina propria. Verhoeff-van Gieson and von Kossa staining confirmed their identity as calcified elastic fibers. A histopathological diagnosis of PXE-like changes was made; the patient was referred to ophthalmology where angioid streaks were visualized fundoscopically. PXE-like changes in the absence of the characteristic genetic mutation have also been reported with or without systemic manifestations. Furthermore, PXE-like changes have been reported in up to 10% of oral biopsy specimens undertaken without clinical suspicion for PXE. Therefore, the significance of such changes in isolation is unclear. Clinicians and pathologists should be aware of the potential oral manifestations of PXE to facilitate prompt diagnosis and subspecialist referral.

How Much Should be Invested in Lung Care Across the WHO European Region? Applying a Monetary Value to Disability-Adjusted Life-Years Within the International Respiratory Coalition's Lung Facts.

OBJECTIVES: The International Respiratory Coalition's Lung Facts web resource provides the latest data on a range of lung conditions covering the World Health Organization's European Region, informed by the Global Burden of Disease studies: https://international-respiratory-coalition.org/lung-facts/ . Within Lung Facts, disability-adjusted life-years (DALYs) are monetised based on gross domestic product (GDP) per capita. We describe the conceptual and empirical basis for using monetised DALYs to inform negotiations with policymakers to invest in lung care across the World Health Organization European region. METHODS: We reflect on the existing debate and research evidence regarding the X value in an X*GDP per capita framework to monetise DALYs, with a focus on if 1*GDP per capita is conceptually and practically appropriate. Using an asthma case study, Global Burden of Disease study 2019 DALY estimates per country are presented. Gross domestic product per capita are converted to international dollars using purchasing power parity (Int$2019). RESULTS: Using 1*GDP per capita, the estimated monetised asthma DALY burden, for example, in Kyrgyzstan or Germany is: across the whole population, $44,860,483 or $9,264,767,882, respectively; per 100,000 people, $731,600 or $10,208,317, respectively. CONCLUSIONS: Our indicative monetised DALY estimates can enable informed discussions with policy and decision makers, to guide financial investment in alleviating the burden of lung conditions. We suggest 1*GDP per capita as a benchmarked value forms a starting point for negotiation with policymakers for investing in lung care, by scaling the estimated lung condition DALY burden to the resource available in each country to tackle the burden.

Synchronous Pancreatic Masses.

Any mass lesion in the pancreas usually raises the possibility of undiagnosed pancreatic cancer. With the advancement of imaging modalities, we are seeing an increasing number of incidental findings, some of which may be clinically significant. When dealing with incidental pancreatic findings, it is critical to keep a broad differential in mind in addition to ruling out pancreatic malignancy. We present 3 rare cases of patients with 2 or more synchronous solid masses in the pancreas caused by pancreatic cancer, type 1 autoimmune pancreatitis, and sarcoidosis.