Patient-Reported Experiences with a Relicensed Generic: Thioguanine for the Treatment of Inflammatory Bowel Diseases.

BACKGROUND AND AIM: Patient-reported outcomes and experiences are indicative of the impact and the quality of care. Thioguanine, a generic drug initially developed for leukemia, has been explored and relicensed as a certified treatment for patients with inflammatory bowel diseases (IBD). The patients' perception of this treatment has not been evaluated before. In this study, we aimed to assess self-reported experiences with thioguanine for IBD. METHODS: Questionnaires were sent out to members of the Dutch National Crohn's and Colitis patient organization. The Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) was used to address questions regarding the satisfaction and impact of thioguanine therapy on the disease and their daily life. Furthermore, data on demographics, disease and (historical) treatment characteristics were collected. Open-ended questions were used for additional comments to the questionnaire. RESULTS: A total of 173 organization members (73% female) reported to be previous or current users of thioguanine. A total of 74% were satisfied with the effectiveness of thioguanine, whereas 5% were not. Eighty percent of the respondents were satisfied with the quality of care. A good or excellent impact on daily life was reported by 54%. A neutral or bad impact on daily life was reported by 40% and 6%, respectively. Improvement of disease activity was reported by 58%. This remained stable or worsened in 39% and 3%, respectively. CONCLUSION: In this self-report survey, among thioguanine treated patients with IBD who had failed with traditional therapies, 80% reported satisfaction with medical care and 74% with the effectiveness of the therapy. In the evaluation of new or rediscovered therapies, patient-reported outcomes and experiences should be considered as a key instrument.

Assessment of the histopathological key features in autoimmune hepatitis.

AIMS: In this study, we aimed to evaluate the use of typical histological features of both the revised original (1999) and simplified (2008) criteria in the diagnosis of autoimmune hepatitis (AIH) in clinical practice. METHODS AND RESULTS: We performed a detailed histopathological evaluation of the pretreatment biopsies of 63 AIH patients, and used biopsies of 62 untreated chronic viral hepatitis patients [hepatitis B (n = 21) or hepatitis C (n = 41)] as a reference cohort. Biopsies were systematically reviewed for inflammation, fibrosis and the presence of interface hepatitis, plasma cells, rosettes and emperipolesis with a well-defined assessment method. AIH biopsies showed more interface hepatitis (87% versus 63%, P = 0.002), more plasma cell-rich infiltrates (48% versus 27%, P = 0.02), more rosettes (49% versus 23%, P = 0.004) and more emperipolesis (78% versus 50%, P = 0.001) than chronic viral hepatitis biopsies. Emperipolesis (P = 0.01) and rosettes (P < 0.01) were superior to plasma cells and interface hepatitis as independent predictors for AIH. Moderate to severe lymphocytic cholangitis was found in 28% of AIH patients. CONCLUSIONS: Emperipolesis and rosette formation are superior histological predictors of AIH than the classic hallmark features of interface hepatitis and plasma cells. In addition, moderate to severe lymphocytic cholangitis does not preclude the diagnosis of AIH.

Guidelines for designing a digestive disease endoscopy unit: report of the World Endoscopy Organization.

A dedicated digestive disease endoscopy unit is structurally and functionally differentiating rapidly as a result of increasing diagnostic and therapeutic possibilities in the last 10-20 years. Publications with practical details are scarce, imposing a challenge in the construction of such a unit. The lack of authoritative information about endoscopy unit design means that architects produce their own design with or without consulting endoscopists working in such a unit. A working group of the World Endoscopy Organization discussed and outlined a practical approach fordesign and construction of a modern endoscopy unit. Designing the layout is extremely important, necessitating thoughtful planning to provide comfort to the endoscopy staff and patients, and efficient data archiving and transmission during endoscopic services.

Anticipating implementation of colorectal cancer screening in The Netherlands: a nation wide survey on endoscopic supply and demand.

BACKGROUND: Colorectal cancer (CRC) screening requires sufficient endoscopic resources. The present study aims to determine the Dutch endoscopic production and manpower for 2009, evaluate trends since 2004, determine additional workload which would be caused by implementation of a CRC screening program, and inventory colonoscopy rates performed in other European countries. METHODS: All Dutch endoscopy units (N = 101) were surveyed for manpower and the numbers of endoscopy procedures performed in 2009. Based on calculations in the report issued by the Dutch Health Council, future additional workload caused by faecal immunochemical test (FIT) screening was estimated. The number of colonoscopies performed in Europe was evaluated by a literature search and an email-inquiry. RESULTS: Compared to 2004, there was a 24% increase in total endoscopies (N = 505,226 in 2009), and a 64% increase in colonoscopies (N = 191,339 in 2009) in The Netherlands. The number of endoscopists had increased by 4.6% (N = 583 in 2009). Five years after stepwise implementation of FIT-based CRC screening, endoscopic capacity needs to be increased an additional 15%. A lack of published data on the number of endoscopies performed in Europe was found. Based on our email-inquiry, the number of colonoscopies per 100,000 inhabitants ranged from 126 to 3,031 in 15 European countries. CONCLUSIONS: Over the last years, endoscopic procedures increased markedly in The Netherlands without a corresponding increase in manpower. A FIT-based CRC screening program requires an estimated additional 15% increase in endoscopic procedures. It is very likely that current colonoscopy density varies widely across European countries.

Gastroenterology in developing countries: issues and advances.

Developing countries shoulder a considerable burden of gastroenterological disease. Infectious diseases in particular cause enormous morbidity and mortality. Diseases which afflict both western and developing countries are often seen in more florid forms in poorer countries. Innovative techniques continuously improve and update gastroenterological practice. However, advances in diagnosis and treatment which are commonplace in the West, have yet to reach many developing countries. Clinical guidelines, based on these advances and collated in resource-rich environments, lose their relevance outside these settings. In this two-part review, we first highlight the global burden of gastroenterological disease in three major areas: diarrhoeal diseases, hepatitis B, and Helicobacter pylori. Recent progress in their management is explored, with consideration of future solutions. The second part of the review focuses on the delivery of clinical services in developing countries. Inadequate numbers of healthcare workers hamper efforts to combat gastroenterological disease. Reasons for this shortage are examined, along with possibilities for increased specialist training. Endoscopy services, the mainstay of gastroenterology in the West, are in their infancy in many developing countries. The challenges faced by those setting up a service are illustrated by the example of a Nigerian endoscopy unit. Finally, we highlight the limited scope of many clinical guidelines produced in western countries. Guidelines which take account of resource limitations in the form of "cascades" are advocated in order to make these guidelines truly global. Recognition of the different working conditions facing practitioners worldwide is an important step towards narrowing the gap between gastroenterology in rich and poor countries.

6-Thioguanine seems promising in azathioprine- or 6-mercaptopurine-intolerant inflammatory bowel disease patients: a short-term safety assessment.

OBJECTIVE: 6-Mercaptopurine (6-MP) and azathioprine (AZA) have proven efficacy in the treatment of inflammatory bowel disease (IBD). However, adverse events leading to discontinuation may occur in 10-20% of patients. The efficacy of AZA and 6-MP is based on formation of their active metabolites, the 6-thioguaninenucleotides (6-TGNs). Therefore, 6-thioguanine (6-TG), an agent leading more directly to the formation of 6-TGNs and until recently used only in patients suffering from leukaemia, may be an alternative in AZA or 6-MP intolerance. The purpose of our study was to assess the short-term safety of 6-TG. METHODS: Thirty-two IBD patients with previously established AZA or 6-MP intolerance were treated with 6-TG in doses of 20 mg (n = 19) or 40 mg (n = 13) once daily. Safety parameters were obtained at 0, 1, 2, 4 and 8 weeks after start of medication. Primary outcome measures were the ability to tolerate 6-TG and the occurrence of adverse events. Secondary outcome definitions included laboratory parameters. RESULTS: Twenty-six (81%) patients were able to tolerate 6-TG during the first 8 weeks. In three of six patients, side effects leading to discontinuation were probably (n = 2) or obviously (n = 1) related to 6-TG. No clinically relevant haematological events or hepatotoxicity occurred in the observed period. Steady-state 6-TG levels were significantly higher with 40 mg once daily (1621 +/- 828 picomol/8 x 10(8) red blood cells (RBC)) than with 20 mg once daily (937 +/- 325 picomol/8 x 10(8) RBC; n = 0.001). CONCLUSIONS: 6-TG treatment seems promising in AZA- or 6-MP-intolerant IBD patients. However, long-term safety and efficacy have yet to be determined.