MATERIAL AND METHOD: A two-round Delphi online questionnaire was completed and validated by international experts to identify consensual items. They were asked to rate the validity of each items taking into account the recommendations and practices in their countries. Only propositions obtaining a median score in the upper tertile with an agreement of more than 75% of the panel-for the first round-and 85%-for the second round-were retained.

RESULTS: Our panel included 11 pharmacists (55%) and 9 physicians (45%). The panelists came from 12 different countries: England, Belgium, Brazil, Canada, China, Ivory Coast, Ireland, Malaysia, Portugal, Switzerland, Turkey and Vietnam. At the end of the first round, of the 105 items of the original POPI tool, 80 items were retained including 16 items reworded and 25 items were deleted. In the second round, 14 experts participated in the study. This final international POPI tool is composed of 73 IP and omissions of prescriptions in the fields of neuropsychiatry, dermatology, infectiology, pneumology, gastroenterology, pain and fever.

AIM: We investigated the association between air pollution exposure and IBD.

METHODS: The European Prospective Investigation into Cancer and Nutrition cohort was used to identify cases with Crohn's disease (CD) (n = 38) and ulcerative colitis (UC) (n = 104) and controls (n = 568) from Denmark, France, the Netherlands, and the UK, matched for center, gender, age, and date of recruitment. Air pollution data were obtained from the European Study of Cohorts for Air Pollution Effects. Residential exposure was assessed with land-use regression models for particulate matter with diameters of <10 μm (PM10), <2.5 μm (PM2.5), and between 2.5 and 10 μm (PMcoarse), soot (PM2.5 absorbance), nitrogen oxides, and two traffic indicators. Conditional logistic regression analyses were performed to calculate odds ratios (ORs) with 95 % confidence intervals (CIs).

RESULTS: Although air pollution was not significantly associated with CD or UC separately, the associations were mostly similar. Individuals with IBD were less likely to have higher exposure levels of PM2.5 and PM10, with ORs of 0.24 (95 % CI 0.07-0.81) per 5 μg/m(3) and 0.25 (95 % CI 0.08-0.78) per 10 μg/m(3), respectively. There was an inverse but nonsignificant association for PMcoarse. A higher nearby traffic load was positively associated with IBD [OR 1.60 (95 % CI 1.04-2.46) per 4,000,000 motor vehicles × m per day]. Other air pollutants were positively but not significantly associated with IBD.

METHODS: The study consists of literature reviews and key stakeholders interviews in six focus countries, including the Philippines, Singapore, Malaysia, Indonesia, Vietnam, and Thailand and five countries as best practice, comprising of France, Canada, Australia, Taiwan, and South Korea. Rare disease management initiatives across each country were examined based on the World Health Organization's framework for action in strengthening health systems.

RESULTS: The results suggest rare disease management remains challenging across Southeast Asia, as many of the focus countries face fundamental issues from basic healthcare systems to funding. Nonetheless, there are substantial improvement opportunities, including leveraging best practices from around the world and organising a multi-stakeholder and regional approach and strategy.

METHODS: This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009.

FINDINGS: Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76-0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74-0·95, 0·85; 95% CI 0·83-0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0.

INTERPRETATION: The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease.