Effects of red meat taxes and warning labels on food groups selected in a randomized controlled trial.

BACKGROUND: High consumption of red and processed meat contributes to both health and environmental harms. Warning labels and taxes for red meat reduce selection of red meat overall, but little is known about how these potential policies affect purchases of subcategories of red meat (e.g., processed versus unprocessed) or of non-red-meat foods (e.g., cheese, pulses) relevant to health and environmental outcomes. This study examined consumer responses to warning labels and taxes for red meat in a randomized controlled trial. METHODS: In October 2021, we recruited 3,518 US adults to complete a shopping task in a naturalistic online grocery store. Participants were randomly assigned to one of four arms: control (no warning labels or tax), warning labels only (health and environmental warning labels appeared next to products containing red meat), tax only (prices of products containing red meat were increased 30%) or combined warning labels + tax. Participants selected items to hypothetically purchase, which we categorized into food groups based on the presence of animal- and plant-source ingredients (e.g., beef, eggs, pulses), meat processing level (e.g., processed pork versus unprocessed pork), and meat species (e.g., beef versus pork). We assessed the effects of the warning labels and tax on selections from each food group. RESULTS: Compared to control, all three interventions led participants to select fewer items with processed meat (driven by reductions in processed pork) and (for the tax and warning labels + tax interventions only) fewer items with unprocessed meat (driven by reductions in unprocessed beef). All three interventions also led participants to select more items containing cheese, while only the combined warning labels + tax intervention led participants to select more items containing processed poultry. Except for an increase in selection of pulses in the tax arm, the interventions did not affect selections of fish or seafood (processed or unprocessed), eggs, or plant-based items (pulses, nuts & seeds, tofu, meat mimics, grains & potatoes, vegetables). CONCLUSIONS: Policies to reduce red meat consumption are also likely to affect consumption of other types of foods that are relevant to both health and environmental outcomes. TRIAL REGISTRATION: NCT04716010 on www. CLINICALTRIALS: gov .

Utilization, Expenditure, and Treatment Patterns Associated With Calcitonin Gene-Related Peptide Monoclonal Antibodies Reimbursed Subject to a Managed Access Protocol in Ireland.

OBJECTIVES: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are novel high-cost treatments for the prevention of migraine. This study presents data on utilization, expenditure, and treatment patterns with CGRP mAbs available under a managed access protocol in Ireland, to a cohort of treatment refractory patients (failed 3 or more previous treatments) with chronic migraine. METHODS: Data were extracted from the Primary Care Reimbursement Service High Tech claims database and special drug request online system and analyzed using Microsoft Excel and SAS. Treatment persistence was evaluated by refill patterns, and adherence was evaluated using the proportion of days covered method. Expenditure data were extracted directly from the database. RESULTS: Between September 1, 2021 and April 30, 2023, 1517 applications for reimbursement approval for a CGRP mAb were received; 1458 (96.1%) were approved for reimbursement. Total expenditure on CGRP mAbs in year 1 (September 1, 2021 to August 31, 2022) was €3.2 million. The majority of patients initiated treatment with fremanezumab (60.8%) or erenumab (37.1%). Almost 90% of patients were considered adherent, and treatment persistence was high, with more than 75% of patients receiving more than 12 months of treatment in our 18-month study time frame. CONCLUSIONS: This study demonstrates the importance of active health technology management, after reimbursement, in enabling cost-effective use of high-cost treatments while providing budget certainty for the healthcare payer. High levels of adherence and persistence suggest that treatment is successfully targeted in situations which unmet clinical need is greatest.

Evaluation and Modification of a Shared Decision-Making Tool for Peanut Allergy Management.

PURPOSE OF REVIEW: Based on shared decision-making (SDM) principles, a decision aid was previously developed to help patients, their caregivers, and physicians decide which peanut allergy management approach best suits them. This study refined the decision aid's content to better reflect patients' and caregivers' lived experience. RECENT FINDINGS: Current standard of care for peanut allergy is avoidance, although peanut oral immunotherapy has been approved by the Food and Drug Administration for use in patients 4-17 years old. An advisory board of allergy therapy experts (n = 3) and patient advocates (n = 3) informed modifications to the decision aid. The revised tool underwent cognitive debriefing interviews (CDIs) among adolescents (12-17 years old) with peanut allergy and caregivers of patients 4-17 years old with peanut allergy to evaluate its relevance, understandability, and usefulness. The 20 CDI participants understood the information presented in the SDM tool and reported it was important and relevant. Some revisions were made based on participant feedback. Results support content validity of the Peanut Allergy Treatment SDM Tool.

Inhibition of discoidin domain receptor (DDR)-1 with nilotinib alters CSF miRNAs and is associated with reduced inflammation and vascular fibrosis in Alzheimer's disease.

Discoidin Domain Receptor (DDR)-1 is activated by collagen. Nilotinib is a tyrosine kinase inhibitor that is FDA-approved for leukemia and potently inhibits DDR-1. Individuals diagnosed with mild-moderate Alzheimer's disease (AD) treated with nilotinib (versus placebo) for 12 months showed reduction of amyloid plaque and cerebrospinal fluid (CSF) amyloid, and attenuation of hippocampal volume loss. However, the mechanisms are unclear. Here, we explored unbiased next generation whole genome miRNA sequencing from AD patients CSF and miRNAs were matched with their corresponding mRNAs using gene ontology. Changes in CSF miRNAs were confirmed via measurement of CSF DDR1 activity and plasma levels of AD biomarkers. Approximately 1050 miRNAs are detected in the CSF but only 17 miRNAs are specifically altered between baseline and 12-month treatment with nilotinib versus placebo. Treatment with nilotinib significantly reduces collagen and DDR1 gene expression (upregulated in AD brain), in association with inhibition of CSF DDR1. Pro-inflammatory cytokines, including interleukins and chemokines are reduced along with caspase-3 gene expression. Specific genes that indicate vascular fibrosis, e.g., collagen, Transforming Growth Factors (TGFs) and Tissue Inhibitors of Metalloproteases (TIMPs) are altered by DDR1 inhibition with nilotinib. Specific changes in vesicular transport, including the neurotransmitters dopamine and acetylcholine, and autophagy genes, including ATGs, indicate facilitation of autophagic flux and cellular trafficking. Inhibition of DDR1 with nilotinib may be a safe and effective adjunct treatment strategy involving an oral drug that enters the CNS and adequately engages its target. DDR1 inhibition with nilotinib exhibits multi-modal effects not only on amyloid and tau clearance but also on anti-inflammatory markers that may reduce cerebrovascular fibrosis.

Female terminalia morphology and cladistic relations among Tok-Tok beetles (Tenebrionidae: Sepidiini).

Tok-tokkies are one of the most iconic lineages within Tenebrionidae. In addition to containing some of the largest darkling beetles, this tribe is recognized for its remarkable form of sexual communication known as substrate tapping. Nevertheless, the phylogenetic relationships within the group remain poorly understood. This study investigates the usefulness of female terminalia morphology for delimiting Sepidiini and reconstructing relationships among it. Data on the structure of the ovipositors, genital tubes and spicula ventrali have been generated for >200 species representing 28 Pimeliinae tribes. This dataset was used in a comparative analysis at the subfamilial level, which resulted in recognition of several unique features of tok-tokkie terminalia. Additionally, new features linking phenotypically challenging tribes also were recovered (Cryptochilini + Idisiini + Pimeliini). Secondly, 23 characters linked to the structure of female terminalia were defined for tok-tok beetles. Cladistic analysis demonstrates the nonmonophyletic nature of most of the recognized subtribes. The morphological dataset was analysed separately and in combination with available molecular data (CAD, Wg, cox1, cox2, 28S). All obtained topologies were largely congruent, supporting the following changes: Palpomodina Kaminski & Gearner subtr.n. is erected to accommodate the genera Namibomodes and Palpomodes; Argenticrinis and Bombocnodulus are transferred from Hypomelina to Molurina; 153 species and subspecies previously classified within Psammodes are distributed over three separate genera (Mariazofia Kaminski nom.n., Piesomera stat.r., Psammodes sens.n.). Psammodes sklodowskae Kaminski & Gearner sp.n. is described. Preliminary investigation of the ovipositor of Mariazofia basuto (Koch) comb.n. was carried out with the application of microcomputed tomography, illuminating the muscular system as a reliable reference point for recognizing homologous elements in highly modified ovipositors.

Essential nutrient element profiles in rice types: a risk-benefit assessment including inorganic arsenic.

Rice is consumed by nearly half of the global population and a significant source of energy and nutrients. However, rice consumption can also be a significant pathway of inorganic arsenic (iAs) exposure, thus requiring a risk-benefit assessment. This study assessed nutrient element (NE) densities in fifty-five rice types (white, brown and wild rice) marketed in the UK. Densities of essential NE were used to rank rice types in meeting daily NE targets under different consumption scenarios through a newly developed optimisation approach. Using iAs data from these rice types, we assessed the margin of exposure (MOE) for low (the UK) and high (Bangladesh) rice intake scenarios. Our results showed that brown and wild rice are significantly higher in many NE and significantly contribute to dietary reference value (DRV). Our modelling showed that switching to brown or wild rice could increase the intake of several essential nutrients by up to eight times that of white rice. Using rice consumption data for mid-to-high-consumption countries, we estimate that brown rice could provide 100 % adult DRV for Fe, Mg, Cr, P and Mo, and substantial contributions for Zn, Se and K. Our results show that the amount of rice primarily determines risk from iAs consumed rather than the type of rice. Therefore, switching from white to brown or wild rice could be beneficial, provided iAs concentration in rice is within the recommended limits.

Do diets with higher carbon footprints increase the risk of mortality? A population-based simulation study using self-selected diets from the USA.

OBJECTIVE: Are diets with a greater environmental impact less healthy? This is a key question for nutrition policy, but previous research does not provide a clear answer. To address this, our objective here was to test whether American diets with the highest carbon footprints predicted greater population-level mortality from diet-related chronic disease than those with the lowest. DESIGN: Baseline dietary recall data were combined with a database of greenhouse gases emitted in the production of foods to estimate a carbon footprint for each diet. Diets were ranked on their carbon footprints and those in the highest and lowest quintiles were studied here. Preventable Risk Integrated Model (PRIME), an epidemiological modelling software, was used to assess CVD and cancer mortality for a simulated dietary change from the highest to the lowest impact diets. The diet-mortality relationships used by PRIME came from published meta-analyses of randomised controlled trials and prospective cohort studies. SETTING: USA. PARTICIPANTS: Baseline diets came from adults (n 12 865) in the nationally representative 2005-2010 National Health and Nutrition Examination Survey. RESULTS: A simulated change at the population level from the highest to the lowest carbon footprint diets resulted in 23 739 (95 % CI 20 349, 27 065) fewer annual deaths from CVD and cancer. This represents a 1·83 % (95 % CI 1·57 %, 2·08 %) decrease in total deaths. About 95 % of deaths averted were from CVD. CONCLUSIONS: Diets with the highest carbon footprints were associated with a greater risk of mortality than the lowest, suggesting that dietary guidance could incorporate sustainability information to reinforce health messaging.

Sacubitril/valsartan (Entresto) utilisation and prescribing patterns in the context of a reimbursement application system.

AIMS: Entresto (sacubitril/valsartan) is used to treat symptomatic chronic heart failure with reduced ejection fraction. Given its high potential budget impact, the Health Services Executive introduced a reimbursement application system (RAS) to ensure its appropriate use. The aim of this study was to evaluate the utilisation of Entresto in Ireland and compare patient characteristics to those of the pivotal PARADIGM-HF trial. METHODS: We used dispensed claims data from the Primary Care Reimbursement Services, clinical data obtained from the RAS, and data from published studies of Entresto utilisation. Differences in the baseline characteristics in the study populations vs the Entresto arm of the PARADIGM-HF trial were analysed. We also investigated cardiovascular medication use in the 6 months pre- and post-Entresto initiation. RESULTS: In 2018, there were 1043 individuals receiving Entresto, corresponding to an expenditure of €1.2 million. Patients prescribed Entresto in Ireland were older, had lower left ventricular ejection fraction and were more symptomatic than those in the PARADIGM-HF trial. Irish patient characteristics were reflective of Entresto-treated populations in other real-world studies. More than 63% of patients were commenced on the lowest Entresto dose. Entresto initiation was associated with a reduction in the use of other medications for heart failure. CONCLUSION: The utilisation of Entresto has been steadily increasing in Ireland since its reimbursement approval. The expenditure in the first year was substantially lower than predicted, and the RAS is an example of how health technology management can facilitate appropriate and cost-effective use of medicines.

Trends in strong opioid prescribing in Ireland: A repeated cross-sectional analysis of a national pharmacy claims database between 2010 and 2019.

PURPOSE: Significant increases in opioid utilisation have been reported in many countries in recent decades. This study investigated strong opioid prescribing in Irish General Medical Services (GMS) patients over a 10-year period. METHODS: A retrospective repeated cross-sectional analysis of a national pharmacy claims database between January 2010 and December 2019 was conducted. Strong opioid prescribing in GMS patients was evaluated, including by route of administration, age (16-64 years and ≥65 years) and gender. Measures of consumption included prescribing prevalence and defined daily dose (DDD)/1000 population/day. Prevalence ratios (PRs) with 95% confidence intervals (CIs), and percentage and absolute changes were determined. RESULTS: Strong opioid prescribing prevalence increased from 14.43% in 2010 to 16.28% in 2019, with the greatest increase in the ≥65 years age group. Tramadol was the most frequently prescribed product, constituting 63.9% of total strong opioid prescribing. The prescribing prevalence of oxycodone increased from 0.95% in 2010 to 2.68% in 2019 (PR 2.81, 95% CI 2.76, 2.87), with steep increases in oxycodone-naloxone since it became available (PR 5.23, 95% CI 4.98, 5.50). The prescribing prevalence of tapentadol increased from 0.18% to 1.58% between 2012 (first complete year available for reimbursement) and 2019 (PR 8.79, 95% CI 8.43, 9.16). Strong opioid prescribing was highest in females aged ≥65 years. CONCLUSIONS: This study found an overall increase in strong opioid prescribing in Ireland between 2010 and 2019, particularly in older adults. Tramadol was the most frequently prescribed product, with oxycodone and tapentadol prescribing increasing markedly over the study period.

Pre-diagnostic statin use, lymph node status and mortality in women with stages I-III breast cancer.

BACKGROUND: Recent meta-analyses suggest that pre-diagnostic statin use is associated with reduced breast cancer-specific mortality. Studies have shown that high breast tumour expression of the statin target (3-hydroxy-3-methylglutaryl coenzyme-A reductase) is associated with lymph-node negative cancer. Therefore, we examined the association between pre-diagnostic statin use and; lymph node status, breast cancer-specific and all-cause mortality. METHODS: Women with stages I-III breast cancer were identified from the National Cancer Registry of Ireland (N=6314). Pre-diagnostic statin users were identified from linked prescription claims data (N=2082). Relative risks were estimated for associations between pre-diagnostic statin use and lymph node status. Hazard ratios (HR) were estimated for associations between pre-diagnostic statin use and breast cancer-specific and all-cause mortality. RESULTS: Pre-diagnostic statin use was not associated with lymph node negative status at diagnosis. In multivariate analyses, pre-diagnostic statin use was associated with reduced all-cause (HR 0.78 95% confidence interval (CI) 0.69, 0.89) and breast cancer-specific mortality (HR 0.81 95% CI 0.68, 0.96). This reduction in cancer-specific mortality was greatest in statin-users with oestrogen (ER) receptor-positive tumours (HR 0.69 95% CI 0.55, 0.85). CONCLUSION: Patients with pre-diagnostic statin exposure had a significant reduction in breast cancer-specific mortality, which was even more pronounced in women with ER+ tumours.

A systematic review and narrative synthesis of group self-management interventions for adults with epilepsy.

BACKGROUND: Epilepsy is a serious and costly long-term condition that negatively affects quality of life, especially if seizures persist on medication. Studies show that people with epilepsy (PWE) want to learn more about the condition and some educational self-management courses have been trialled internationally. The objectives of this review were to evaluate research and summarise results on group self-management interventions for PWE. METHODS: We searched Medline and PsycINFO for results published in English between 1995 and 2015. Only studies evaluating face-to-face, group interventions for adults with epilepsy were included. Heterogeneity in study outcomes prevented the carrying out of a meta-analysis; however, a Cochrane style review was undertaken. RESULTS: We found eleven studies, nine of which were randomised controlled trials. There were variable standards of methodological reporting with some risk of bias. Seven of the studies used quality of life as an outcome, with four finding statistically significant improvements in mean total score. Two found an improvement in outcome subscales. One study included some additional semi-qualitative data. CONCLUSIONS: We identified promising trends in the trials reviewed. In particular, there were significant improvements in quality of life scales and seizure frequency in many of the interventions. However, considerable heterogeneity of interventions and outcomes made comparison between the studies difficult. Courses that included psychological interventions and others that had a high number of sessions showed more effect than short educational courses. Furthermore, the evidence was predominantly from pilot studies with small sample sizes and short follow-up duration. Further research is needed to better evaluate the role of group self-management interventions in outpatient epilepsy management.

Patterns of statin initiation and continuation in patients with breast or colorectal cancer, towards end-of-life.

PURPOSE: Cross-sectional studies show that statins, used in cardiovascular disease prevention, are often discontinued approaching death. Studies investigating associations between statin exposure and cancer outcomes, not accounting for these exposure changes, are prone to reverse causation bias. The aim of this study was to describe longitudinally the changes in statin initiation and continuation prior to death in patients with breast or colorectal cancer, thus establishing an appropriate exposure lag time. METHODS: This study was carried out using linked cancer registry and prescribing data. We identified patients who died of their cancer (cases) and cancer survivors were used as controls. The probability of initiating or continuing statin use was estimated up to 5 years prior to death (or index date). Conditional binomial models were used to estimate relative risks and risk differences for associations between approaching cancer death and statin use. RESULTS: Compared to controls, the probability of continued statin use in breast cancer cases was significantly lower 3 months prior to death (RR 0.86 95% CI 0.79, 0.94). Similarly, in colorectal cancer cases, the probability of continued statin use was significantly lower 3 months prior to colorectal cancer death (RR 0.77 95% CI 0.68, 0.88). CONCLUSION: A significant proportion of patients will cease statin treatment in the months prior to a colorectal or breast cancer death.

Linking ecosystem service supply to stakeholder concerns on both land and sea: An example from Guánica Bay watershed, Puerto Rico.

Policies to protect coastal resources may lead to greater social, economic, and ecological returns when they consider potential co-benefits and trade-offs on land. In Guánica Bay watershed, Puerto Rico, a watershed management plan is being implemented to restore declining quality of coral reefs due to sediment and nutrient runoff. However, recent stakeholder workshops indicated uncertainty about benefits for the local community. A total of 19 metrics were identified to capture stakeholder concerns, including 15 terrestrial ecosystem services in the watershed and 4 metrics in the coastal zone. Ecosystem service production functions were applied to quantify and map ecosystem service supply in 1) the Guánica Bay watershed and 2) a highly engineered upper multi-watershed area connected to the lower watershed via a series of reservoirs and tunnels. These two watersheds were compared to other watersheds in Puerto Rico. Relative to other watersheds, the Upper Guánica watershed had high air pollutant removal rates, forest habitat area, biodiversity of charismatic and endangered species, but low farmland quality and low sediment retention. The Lower Guánica watershed had high rates of denitrification and high levels of marine-based recreational and fishing opportunities compared to other watersheds, but moderate to low air pollutant removal, soil carbon content, sediment and nutrient retention, and terrestrial biodiversity. Our results suggest that actions in the watershed to protect coral reefs may lead to improvements in other ecosystem services that stakeholders care about on land. Considering benefits from both coastal and terrestrial ecosystems in making coastal management decisions may ultimately lead to a greater return on investment and greater stakeholder acceptance, while still achieving conservation goals.

De novo post-diagnosis statin use, breast cancer-specific and overall mortality in women with stage I-III breast cancer.

BACKGROUND: Prior evidence suggests a role for statins in the management of cancer. However, the benefit of statin use in the adjuvant setting remains uncertain. This study investigates associations between statin use initiated after a breast cancer diagnosis and mortality. METHODS: Women with stage I-III breast cancer were identified from the National Cancer Registry of Ireland (N=4243). Post-diagnostic statin initiators were identified from pharmacy claims data (N=837). Multivariate models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between de novo statin use and mortality. RESULTS: The median duration of statin use was 6.7 years. No association was found between post-diagnostic statin use and breast cancer-specific (HR 0.88, 95% CI 0.66, 1.17) or all-cause mortality (HR 1.00, 95% CI 0.82, 1.21). CONCLUSIONS: The results from our study suggest that initiating statin use after a diagnosis of stage I-III breast cancer is not associated with a reduction in breast cancer-specific mortality.

Associations Between the KIAA0319 Dyslexia Susceptibility Gene Variants, Antenatal Maternal Stress, and Reading Ability in a Longitudinal Birth Cohort.

Maternal stress during pregnancy has been associated with detrimental cognitive developmental outcomes in offspring. This study investigated whether antenatal maternal perceived stress and variants of the rs12193738 and rs2179515 polymorphisms on the KIAA0319 gene interact to affect reading ability and full-scale IQ (FSIQ) in members of the longitudinal Auckland Birthweight Collaborative study. Antenatal maternal stress was measured at birth, and reading ability was assessed at ages 7 and 16. Reading data were available for 500 participants at age 7 and 479 participants at age 16. FSIQ was measured at ages 7 and 11. At age 11, DNA samples were collected. Analyses of covariance revealed that individuals with the TT genotype of the rs12193738 polymorphism exposed to high maternal stress during pregnancy possessed significantly poorer reading ability (as measured by Woodcock-Johnson Word Identification standard scores) during adolescence compared with TT carriers exposed to low maternal stress. TT carriers of the rs12193738 SNP also obtained lower IQ scores at age 7 than C allele carriers. These findings suggest that the KIAA0319 gene is associated with both reading ability and general cognition, but in different ways. The effect on IQ appears to occur earlier in development and is transient, whereas the effect of reading ability occurs later and is moderated by antenatal maternal stress. Copyright © 2016 John Wiley & Sons, Ltd.

10 Years Later: Changes in Food Access Disparities in New Orleans since Hurricane Katrina.

Inadequate access to healthy food is a problem in many urban neighborhoods, particularly for racial-ethnic minorities and low-income groups who are more likely to reside in food deserts. Although substantial research throughout the country has documented the existence of these disparities, few studies have focused on how this access changes over time or is affected by environmental shocks. This study examined citywide supermarket access in New Orleans as well as racial-ethnic disparities in this access, prior to Hurricane Katrina and at three times afterwards. On-the-ground verification of supermarket locations was conducted in 2004-2005, 2007, 2009, and 2014 and was mapped with secondary demographic data. Census tracts were defined as predominantly African-American neighborhoods if 80 % or more of the population identified as such. HLM Poisson regression analyses were conducted in 2014 to identify the difference in likelihood of finding supermarkets in a neighborhood by race-ethnicity and across all years of interest. Racial-ethnic disparities existed before the storm and worsened after it (IRR = 0.35; 95 % CI = 0.21, 0.60). Improvements in disparities to pre-storm levels were not seen until 2009, 4 years after the storm. By 2014, supermarket access, on average, was not significantly different in African-American neighborhoods than in others (IRR = 0.90; 95 % CI = 0.65, 1.26). The slow recovery of New Orleans' retail food infrastructure after Hurricane Katrina highlights the need for an increased focus on long-term planning to address disparities, especially those that may be exaggerated by shocks.

Utilising Health Technology Assessment to Develop Managed Access Protocols to Facilitate Drug Reimbursement in Ireland.

The Health Service Executive, responsible for operating the Irish health service, has introduced health technology management (HTM) initiatives to manage expenditure on medicines. One such approach is managed access protocols (MAPs) to support access to high-cost medicines, while providing oversight, governance and budgetary certainty to the payer. Herein we describe the development and operation of MAPs, using case studies of liraglutide (Saxenda®), dupilumab (Dupixent®) and calcitonin gene-related peptide monoclonal antibodies. A MAP imposes the eligibility criteria attached to reimbursement support of a medicine. Criteria applied include controls on prescribing authority, clinical diagnostic and severity criteria, previous lines of treatment, concomitant treatments, outcome data collection, and validations within the reimbursement claims system. The choice of criteria are specific to each medicine, dictated by the areas of uncertainty highlighted in the health technology assessment report, such as the place in treatment, population, duration of treatment, etc., the commercial arrangements reached with the marketing authorisation holder, and specific recommendations made by the decision maker. By December 2023, there were 28 medicines reimbursed subject to a MAP in Ireland. Across the three case studies outlined, over 3000 patients were accessing novel treatments for chronic illnesses in September 2023. Managed access protocols can provide some cost certainty for the payer by aligning utilisation and expenditure with committed funds, while enabling access where unmet need is highest. Managed access protocols are now established in the drug reimbursement process in Ireland, meeting the needs of both payers, patients and industry, and are likely to remain a feature of the reimbursement landscape.

Popular diets as selected by adults in the United States show wide variation in carbon footprints and diet quality.

BACKGROUND: Carbon footprints of vegetarian, pescatarian, and other popular diets have been studied previously, but mostly as idealized versions modeled to meet dietary recommendations. Less is known about the footprints of popular diets as they are consumed by US adults, and thus the potential trade-offs with diet quality for free-living individuals. OBJECTIVES: This study estimated the carbon footprint and diet quality of popular diets as selected by a nationally representative sample of US consumers, including the recently trending keto- and paleo-style diets. METHODS: The 2005-2010 NHANES 24-h recall data were used to categorize individual adult diets (n = 16,412) into 6 types: vegan, vegetarian, pescatarian, paleo, keto, and all other diets, referred to here as omnivore diets. Average daily greenhouse gas emissions in kilograms of carbon dioxide equivalents per 1000 kcal (kg CO2-eq/1000 kcal) were calculated for each diet by matching our previously developed database to NHANES individual diet data. Diet quality was determined using the Healthy Eating Index (HEI) and the Alternate Healthy Eating Index. Survey-weighted ordinary least-squares regression was used to assess mean differences in diets. RESULTS: The average carbon footprints of vegan (0.69 ± 0.05 kg CO2-eq/1000 kcal) and vegetarian (1.16 ± 0.02) diets were lower (P < 0.05) than those of the pescatarian (1.66 ± 0.04), omnivore (2.23 ± 0.01), paleo (2.62 ± 0.33), or keto (2.91 ± 0.27) diets. Mean HEI scores were highest for pescatarian diets (58.76 ± 0.79) and higher (P < 0.05) for vegetarian (51.89 ± 0.74) than for omnivore (48.92 ± 0.33) or keto (43.69 ± 1.61) diets. CONCLUSIONS: Our results highlight the nuances when evaluating the nutritional quality of diets and their carbon footprints. On average, pescatarian diets may be the healthiest, but plant-based diets have lower carbon footprints than other popular diets, including keto- and paleo-style diets.

Demographic and Socioeconomic Correlates of Disproportionate Beef Consumption among US Adults in an Age of Global Warming.

Concern for the environment when making dietary choices has grown as the contribution of the food sector to global greenhouse gas emissions becomes more widely known. Understanding the correlates of beef eating could assist in the targeting of campaigns to reduce the consumption of high-impact foods. The objective of this study was to identify the demographic, socioeconomic, and behavioral correlates of disproportionate beef consumption in the United States. We analyzed 24-h dietary recall data from adults (n = 10,248) in the 2015-2018 National Health and Nutrition Examination Survey (NHANES). Disproportionate beef consumption was defined as an intake greater than four ounce-equivalents per 2200 kcal. Associations of this indicator variable with gender, age, race/ethnicity, education, family income, diet knowledge, and away-from-home meals were assessed using logistic regression, incorporating survey design and weighting. Disproportionate beef diets were consumed by 12% of individuals, but accounted for half of all beef consumed. Males were more likely than females (p < 0.001) to consume these diets. This relationship was seen in all bivariate and multivariable models. Older adults, college graduates, and those who looked up the MyPlate educational campaign online were less likely (p < 0.01) to consume a disproportionate beef diet. While almost one-third of reported consumption came from cuts of beef (e.g., steak or brisket), six of the top ten beef sources were mixed dishes: burgers, meat mixed dishes, burritos and tacos, frankfurters, soups, and pasta. Efforts to address climate change through diet modification could benefit from targeting campaigns to the highest consumers of beef, as their consumption accounts for half of all beef consumed.

Malignant Progression of an Ancestral Bone Marrow Clone Harboring a CIC-NUTM2A Fusion in Isolated Myeloid Sarcoma.

Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute myeloid leukemia or, in the absence of bone marrow involvement. We identified an infant with isolated myeloid sarcoma whose bone marrow was negative for involvement by flow cytometry. Sequencing revealed the fusion oncogene CIC-NUTM2A and identified the sarcoma to be clonally evolved from the bone marrow, which carried the fusion despite the absence of pathology. Murine modeling confirmed the ability of the fusion to transform hematopoietic cells and identified receptor tyrosine kinase (RTK) signaling activation consistent with disruption of the CIC transcriptional repressor. These findings extend the definition of CIC-rearranged malignancies to include hematologic disease, provide insight into the mechanism of oncogenesis, and demonstrate the importance of molecular analysis and tracking of bone marrow involvement over the course of treatment in myeloid sarcoma, including patients that lack flow cytometric evidence of leukemia at diagnosis. IMPLICATIONS: This study illustrates molecular involvement of phenotypically normal bone marrow in myeloid sarcoma, which has significant implications in clinical care. Further, it extends the definition of CIC-rearrangements to include hematologic malignancies and shows evidence of RTK activation that may be exploited therapeutically in cancer(s) driven by these fusions.