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Nonalcoholic fatty liver disease (NAFLD) is associated with substantial morbidity, mortality, and economic burden. With currently no approved treatment, an effective pharmaceutical intervention for this disease must be both clinically- and cost-effective. A Markov model was constructed to estimate the clinical outcomes, costs, and quality of life impact of a hypothetical pharmaceutical intervention. Lifetime clinical outcomes, life-years, quality-adjusted life-years (QALYs), costs (2020 $US), incremental cost-effectiveness ratios (ICERs), and economically justifiable prices (EJPs) were quantified. Only patients with fibrosis stage F2–F4 were assumed eligible to initiate pharmaceutical treatment. Over a mean life expectancy of approximately 21 years in the simulated cohort, drug treatment reduced liver-related mortality by 6.0% (2.7% absolute reduction). Assuming an annual drug cost of $36,000, total discounted medical costs were $574,238 and $120,312 for drug and usual care, respectively, with discounted QALYs estimated to be 9.452 and 9.272 for the two comparators. This yielded an ICER of $2,517,676/QALY gained. The EJP of the drug at an ICER threshold of $150,000/QALY gained was $2,633, a 93% reduction from a base case. Sensitivity analyses suggest that, without a substantial decrease in the drug price, ICERs would exceed $500,000/QALY gained even with the most favorable efficacy assumptions. For a pharmaceutical intervention to be considered cost-effective in the NAFLD fibrosis population, the substantial clinical benefit will need to be coupled with a modest annual price. Annual drug costs exceeding $12,000 likely will not provide reasonable value, even with favorable efficacy. More work is needed to estimate the cost-effectiveness of lifestyle modifications.

Steve Duff,1 Michael S Mafilios,2 Prajakta Bhounsule,3 James T Hasegawa31Veritas Health Economics Consulting, Carlsbad, CA, USA; 2Health Economics Associates, San Diego, CA, USA; 3Health Economics and Reimbursement, Abbott Vascular, Santa Clara, CA, USAAbstract: Peripheral arterial disease is a chronic vascular disease characterized by impaired circulation to the lower extremities. Its most severe stage, known as critical limb ischemia (CLI), puts patients at an increased risk of cardiovascular events, amputation, and death. The objective of this literature review is to describe the burden of disease across a comprehensive set of domains—epidemiologic, clinical, humanistic, and economic—focusing on key studies published in the last decade. CLI prevalence in the United States is estimated to be approximately 2 million and is likely to rise in the coming years given trends in important risk factors such as age, diabetes, and smoking. Hospitalization for CLI patients is common and up to 60% are readmitted within 6 months. Amputation rates are unacceptably high with a disproportionate risk for certain demographic and socioeconomic groups. In addition to limb loss, CLI patients also have reduced life expectancy with mortality typically exceeding 50% by 5 years. Given the poor clinical prognosis, it is unsurprising that the quality of life burden associated with CLI is significant. Studies assessing quality of life in CLI patients have used a variety of generic and disease-specific measures and all document a substantial impact of the disease on the patient’s physical, social, and emotional health status compared to population norms. Finally, the poor clinical outcomes and increased medical resource use lead to a considerable economic burden for national health care systems. However, published cost studies are not comprehensive and, therefore, likely underestimate the true economic impact of CLI. Our summary documents a sobering assessment of CLI burden—a poor clinical prognosis translating into diminished quality of life and high costs for millions of patients. Continued prevention efforts and improved treatment strategies are the key to ameliorating the substantial morbidity and mortality associated with this disease.Keywords: critical limb ischemia, peripheral arterial disease, burden, amputation, quality of life, economics

A collection of folklore and local history stories from Skerries (St. Patrick's : Boys) (school) (Skerries, Co. Dublin), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher T. Mc Namee., Local Ruins - Church Island -- Local Ruins - St Mobhi's Oratory -- Local Ruins - The Monastery at Holmpatrick -- Local Ruins - Baldungan Castle (in the Townland of Hacketstown) -- Local Ruins - The Monastery at Holmpatrick -- In the Penal Times -- Thatched Chapel -- Holy Wells / Pratt, George -- Story about St Moibhi’s Graveyard / Derham, Leo -- Patron Saint of Skerries / Derham, Leo -- Festival Customs - St Stephen's Night / Pratt, George -- Festival Customs - 1st May / Pratt, George -- Festival Customs - Shrove Tuesday / Pratt, George -- Festival Customs - Hallow Eve / Pratt, George -- Local Forge / Pratt, George -- Clothes Made Locally / Pratt, George -- My Home District / Fox, John -- Weather-Lore / Pratt, George -- Riddles / Pratt, George -- Bird-Lore / Hoey, Michael -- Local Happenings / Pratt, George -- Local Roads / Hoey, Michael -- Old Crafts - Basket-Making / Hoey, Michael -- Old Crafts - Thatching / Fox, John -- Story / Pratt, George -- Hidden Treasure / Pratt, George -- Travelling Folk / Reynolds, Joe -- Care of Our Farm Animals / Fox, John -- Stories of the Holy Family / Fox, John -- Stories of the Holy Family / Pratt, George -- Old Paths / Pratt, George -- Old Irish Tale / Hoey, Michael -- Old Irish Tale / Hoey, Michael -- Old Story / Hoey, Michael -- Funny Story / Fox, John -- Local Cures / Fox, John -- Toys Made Locally / Fox, John -- Local Cures / Potter, Desmond -- Homemade Toys / Potter, Desmond -- Old Crafts - Thatching / Fox, John -- Old Graveyards / Fox, John -- Bread / Fox, John -- Old Superstitions / Reynolds, Joe -- Riddles / Fox, John -- Old Prayer / Potter, Desmond -- Fairs and Markets -- Story / Pratt, George -- Story about the Fairies / Pratt, George -- Story / Pratt, George -- Story (The Smugglers' Cave) / Pratt, George -- Stories about the Fairies / Pratt, George -- Story about a Haunted House / Pratt, George -- Kenure Graveyard / Pratt, George -- Story about a Haunted House / Pratt, George -- Kenure Graveyard / Pratt, George -- Planting of the Potato Crop / Pratt, George -- Story about the Fairies / Fox, John -- Digging of the Potato Crop / Fox, John -- Local Place Names / Fox, John -- Story (Strange Happening) / Fox, John -- Story about the Fairies / Fox, John -- Story (The Ladies' Stairs) / Fox, John -- Customs / Fox, John -- Games I Play / Fox, John -- Local Place Names / Fox, John -- Story about St Colmcille / Fox, John -- Local Happenings / Grimes, Michael -- Old Story - Skerries, Co. Dublin / Fox, John -- Local Heroes / Duff, Steve -- Local Wedding Customs / Duff, Steve -- Collection of Riddles / Grimes, Michael -- Story (Old Tale) / Fox, John -- Buying and Selling / Fox, John -- Herbs / Fox, John -- Local Poets / Fox, John -- Story / Fox, John -- Severe Weather / Grimes, Robert -- Story / Fox, John -- Local Landlord / Derham, Leo -- Local Landlord / Namee, Brendan Mc -- Story about a Ghost / Fox, John -- Story / Fox, John -- Story (Collier the Robber) / Fox, John -- Local Cures / Fox, John -- Objects of Value / Namee, Brendan Mc -- Care of the Potatoes / Hoey, Michael -- Story / Potter, Desmond -- Story / Potter, Desmond -- Care of the Feet / Potter, Desmond -- Superstitions / Fox, John -- Story / Derham, Leo -- Food in the Olden Times / Potter, Desmond -- Story / Namee, Brendan Mc -- Gombeen Man / Namee, Brendan Mc -- Stories of the Holy Family / Hoey, Michael, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.