Search

Detailed, country‐specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7001000 cases) and Indonesia (3187000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV‐related mortality and morbidity. HCV‐related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV‐infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV‐related morbidity and mortality are to be achieved.

Gilead Sciences The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. in addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing. Ctr Dis Anal, Louisville, CO 80027 USA Natl Liver Inst, Menoufia, Egypt JW Goethe Univ Hosp, Frankfurt, Germany Univ Calgary, Liver Unit, Div Gastroenterol & Hepatol, Calgary, AB, Canada Ankara Univ, Dept Gastroenterol, Sch Med, TR-06100 Ankara, Turkey Hosp Santo Antonio Capuchos, Dept Gastroenterol, Ctr Hosp Lisboa Cent, Lisbon, Portugal Med Univ Innsbruck, A-6020 Innsbruck, Austria Univ São Paulo, Sch Med, São Paulo, Brazil Hop Henri Mondor, Serv Hepatogastroenterol, F-94010 Creteil, France Adv Tech Hlth Serv Res TAISS, Madrid, Spain Ege Univ, Izmir, Turkey Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden Karolinska Univ Hosp, Dept Gastroenterol & Hepatol Infect Dis, Stockholm, Sweden Ankara Univ, TR-06100 Ankara, Turkey Univ Leipzig, D-04109 Leipzig, Germany Osped Cantonale, Dept Gastroenterol, Bellinzona, Switzerland Univ Montreal, Dept Med, Liver Unit, Montreal, PQ H3C 3J7, Canada Fed Univ State Rio de Janeiro, Dept Gastroenterol, Rio de Janeiro, Brazil Arud Ctr Addict Med, Zurich, Switzerland Hosp Valle de Hebron, CIBERehd, Barcelona, Spain Hosp Puerta Hierro, Madrid, Spain Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense, Denmark Reg Hosp Hovedstaden, Copenhagen, Denmark Univ Fed Rio de Janeiro, Dept Clin Med, Rio de Janeiro, Brazil Univ Plymouth, Peninsula Sch Med & Dent, Plymouth PL4 8AA, Devon, England Univ New S Wales, Kirby Inst, Sydney, NSW, Australia Cairo Univ, Cairo, Egypt Orebro Univ Hosp, Dept Infect Dis, Orebro, Sweden Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden Ain Shams Univ, Cairo, Egypt Dokuz Eylul Univ, Izmir, Turkey Karolinska Inst, Karolinska Univ Hosp, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden Exigo Consultores, Alhos Vedros, Portugal Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic Hosp Carlos III, CIBERehd, Madrid, Spain Univ Copenhagen, Copenhagen, Denmark Direccao Geral Saude, Lisbon, Portugal Univ Estadual Campinas, Disciplina Doencas Infecciosas, Dept Clin Med, Grp Estudo Hepatites,Fac Ciencias Med,UNICAMP, São Paulo, Brazil Wilhelminenspital Stadt Wien, Dept Internal Med 4, Vienna, Austria Univ São Paulo, Sch Med, Div Gastroenterol & Hepatol, São Paulo, Brazil Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Vienna, Austria Masaryk Univ, Univ Hosp Brno, Clin Infect Dis, Brno, Czech Republic Univ Manitoba, Dept Internal Med, Sect Hepatol, Winnipeg, MB, Canada Hlth Sci Ctr, Viral Hepatitis Invest Unit, Winnipeg, MB, Canada European Liver Patients Assoc, St Truiden, Belgium Istanbul Univ, Istanbul, Turkey Univ British Columbia, British Columbia Ctr Dis Control, Vancouver, BC V5Z 1M9, Canada Aalborg Univ Hosp, Dept Med Gastroenterol, Aalborg, Denmark Aalborg Univ Hosp, Sect Mol Diagnost, Aalborg, Denmark Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium Hosp Santa Maria, Dept Gastroenterol, Ctr Hosp Lisboa Norte, Lisbon, Portugal Univ Western Ontario, Div Gastroenterol, London, ON, Canada Univ Dusseldorf, Dusseldorf, Germany Univ Libre Brussels, Erasme Univ Hosp, Brussels, Belgium Univ Hosp, Div Gastroenterol & Hepatol, Geneva, Switzerland Univ Hosp, Div Clin Pathol, Geneva, Switzerland Natl Inst Publ Hlth, Natl Reference Lab Hepatitis, Prague, Czech Republic Univ Southhampton, Southampton, England Dalhousie Univ & Hepatol Serv, Capital Dist Hlth Author, Queen Elizabeth II Hlth Sci Ctr, Dept Med, Halifax, NS, Canada Dalhousie Univ & Hepatol Serv, Capital Dist Hlth Author, Queen Elizabeth II Hlth Sci Ctr, Dept Surg, Halifax, NS, Canada Univ British Columbia, Dept Gastroenterol, Vancouver, BC V5Z 1M9, Canada Assembleia Republ, Lisbon, Portugal Alfred Hosp, Melbourne, Vic, Australia Monash Univ, Melbourne, Vic 3004, Australia UCL, Div Med, UCL Inst Liver & Digest Hlth, London, England Hop Henri Mondor, Dept Sante Publ, F-94010 Creteil, France Nottingham Univ Hosp NHS Trust, Nottingham, England Biomed Res Unit, Nottingham, England Ctr Hosp Porto, Dept Infect Dis, Oporto, Portugal Cantonal Hosp St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 1L7, Canada Egyptian Liver Res Inst & Hosp, Dakahliah, Egypt Monash Hlth, Melbourne, Vic, Australia Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium Med Univ Graz, Div Gastroenterol & Hepatol, Dept Internal Med, Graz, Austria St Vincents Hosp, Dept Gastroenterol, Melbourne, Vic, Australia Univ Melbourne, Melbourne, Vic, Australia Charles Univ Prague, Dept Internal Med, Fac Med 1, Prague, Czech Republic Cent Mil Hosp, Prague, Czech Republic Univ Antwerp, B-2020 Antwerp, Belgium Deutsch Leberhilfe eV, Cologne, Germany Ghent Univ Hosp, Ghent, Belgium Univ Ghent, Belgium Hasselt Univ, Dept Hlth Econ & Patient Safety, Diepenbeek, Belgium Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany Copenhagen Univ Hosp, Hvidovre, Denmark Univ New S Wales, St George Hosp Clin Sch Med, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Univ Zurich Hosp, Swiss HPB Hepatopancreatobiliary Ctr, CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Web of Science

If atom assignment onto 3D molecular graphs is to be optimized, an efficient scheme for placement must be developed. The strategy adopted in this paper is to analyze the molecular graphs in terms of cyclical and non-cyclical nodes; the latter are further divided into terminal and non-terminal nodes. Molecular fragments, from a fragments database, are described in a similar way. A canonical numbering scheme for the fragments and the local subgraph of the molecular graph enables fragments to be placed efficiently onto the molecular graph. Further optimization is achieved by placing similar fragments into bins using a hashing scheme based on the canonical numbering. The graph perception algorithm is illustrated in detail.

Neuroendocrine tumours are a heterogeneous group including, for example, carcinoid, gastroenteropancreatic neuroendocrine tumours, pituitary tumours, medullary carcinoma of the thyroid and phaeochromocytomas. They have attracted much attention in recent years, both because they are relatively easy to palliate and because they have indicated the chronic effect of the particular hormone elevated. As neuroendocrine phenotypes became better understood, the definition of neuroendocrine cells changed and is now accepted as referring to cells with neurotransmitter, neuromodulator or neuropeptide hormone production, dense-core secretory granules, and the absence of axons and synapses. Neuroendocrine markers, particularly chromogranin A, are invaluable diagnostically. Study of several neuroendocrine tumours has revealed a genetic etiology, and techniques such as genetic screening have allowed risk stratification and prevention of morbidity in patients carrying the particular mutation. Pharmacological therapy for these often slow-growing tumours, e.g. with somatostatin analogues, has dramatically improved symptom control, and radiolabelled somatostatin analogues offer targeted therapy for metastatic or inoperable disease. In this review, the diagnosis and management of patients with carcinoid, gut neuroendocrine tumours, multiple endocrine neoplasia types 1 and 2, and isolated phaeochromocytoma are evaluated.

Summary Aims To examine the scope for cardiovascular disease risk factor intervention among diabetic patients in England was examined using data from the Health Surveys for England 1991–94. This evaluation included calculating the proportion who require lipid lowering therapy according to the Standing Medical Advisory Committee (SMAC) guidelines. Methods The Health Survey for England is an annual, nationwide household-based in which anthropomorphic data, blood pressure, lipids and details of cardiovascular risk factors are collected from households after random stratification for geographical and socio-economic factors within a population sample of 39 639 adults, 970 (2.3%) diabetic subjects were identified. Results Overall, 51% of those with diabetes had hypertension (systolic blood pressure ≥ 160 mmHg or a diastolic BP ≥ 95 mmHg or being on antihypertensive therapy), 27% were obese (body mass index ≥ 30 kg/m2) and 19% were current smokers. One-third of those with hypertension were untreated and less than one-half of those on treatment had their hypertension controlled to below 160/95 mmHg. More than one-quarter had poor glycaemic control (glycated Hb > 11% or an HbA1c > 7.5%). Of those aged

This paper is the first of a series which examines the problems of atom assignment in automated de novo drug design. In subsequent papers, a combinatoric optimization method for fragment placement onto 3D molecular graphs is provided. Molecules are built from molecular graphs by placing fragments onto the graph. Here we examine the transferability of atomic residual charge, by fragment placement, with respect to the electrostatic potential. This transferability has been tested on 478 molecular structures extracted from the Cambridge Structural Database. The correlation found between the electrostatic potential computed from composite fragments and that computed for the whole molecule was encouraging, except for extended conjugated systems.

This paper extends an application of the method of simulated annealing for molecular matching so that the best common subsets of atom positions can be identified. Null correspondences are introduced into the difference distance matrix to enable poorly matched positions to be ignored in minimizing the objective function. The efficiency of the algorithm in finding correct subsets is rigorously tested.