Close contacts with leprosy in newly diagnosed leprosy patients in a high and low endemic area:Comparison between Bangladesh and Thailand

Background: As part of a larger study of the role of close contacts in the transmission of M. leprae, we explored whether the proportion of newly detected cases with a family history of leprosy differs with different incidence rates of leprosy in a population. Methods: Retrospective analysis was performed of contacts of all new leprosy patients diagnosed during a 10-yr period in well-established leprosy control programs in Thailand and Bangladesh. By our definition, a contact group consisted of the new case and of past and present cases who were relatives and in-laws of the new case. For a new case, the nearest index case was defined on the basis of time of onset of symptoms for the cases in the contact group, in combination with the level of closeness of contact between these cases and the new case. Three contact levels were distinguished. In Bangladesh these levels were defined as 'kitchen contact'; 'house contact'; and 'non-house contact'. In Thailand comparable levels were defined as 'house contact'; 'compound contact'; and 'neighbor contact'. Results: In Bangladesh 1333, and in Thailand 129 new patients were included. The average new case detection rate over 10 yrs was 50 per 100,000 general population per year in Bangladesh, and 1.5 per 100,000 in Thailand. In the high endemic area 25% of newly detected cases were known to belong to a contact group and were not the index case of this group, whereas in the low endemic area 62% of newly detected cases had these characteristics. The distribution of the nearest index cases over the three contact levels was comparable in both areas. Just over half of the nearest index cases were found within the immediate family unit ('kitchen' in Bangladesh; 'house' in Thailand). Conclusion: The results indicate that in a low endemic area a higher proportion of newly detected leprosy cases have a family history of leprosy compared to a high endemic area. Different contact levels and their relative risks to contract leprosy need to be established more precisely. In high endemic situations the circle of contacts that should be surveyed may need to be wider than currently practiced.</p

CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population

Item does not contain fulltextPURPOSE: Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population. METHODS: In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas. RESULTS: In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma >/=10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88-96) vs. 96% (95% CI: 93-99) for colonoscopy (P = 0.26). For adenomas and carcinomas >/=10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89-97) vs. 97% (95% CI: 94-99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas >/=10 mm was 95% (95% CI: 91-99) for CTC vs. 99% (95% CI: 98-100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86-95) and 96% (95% CI: 94-99), respectively (P < 0.001). CONCLUSION: CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions.1 december 201

T is associated with severe dyspepsia

Contains fulltext : 96333.pdf (publisher's version ) (Open Access

Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H-2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary-care-based randomised controlled trial

Background Substantial physician workload and high costs are associated with the treatment of dyspepsia in primary health care. Despite the availability of consensus statements and guidelines, the most cost-effective empirical strategy for initial management of the condition remains to be determined. We compared step-up and step-down treatment strategies for initial management of patients with new onset dyspepsia in primary care. Methods Patients aged 18 years and older who consulted with their family doctor for new onset dyspepsia in the Netherlands were eligible for enrolment in this double-blind, randomised controlled trial. Between October, 2003, and January, 2006, 664 patients were randomly assigned to receive stepwise treatment with antacid, H-2-receptor antagonist, and proton pump inhibitor (step-up; n=341), or these drugs in the reverse order (step-down; n=323), by use of a computer-generated sequence with blocks of six. Each step lasted 4 weeks and treatment only continued with the next step if symptoms persisted or relapsed within 4 weeks. Primary outcomes were symptom relief and cost-effectiveness of initial management at 6 months. Analysis was by intention to treat (ITT); the ITT population consisted of all patients with data for the primary outcome at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00247715. Findings 332 patients in the step-up, and 313 in the step-down group reached an endpoint with sufficient data for evaluation; the main reason for dropout was loss to follow-up. Treatment success after 6 months was achieved in 238 (72%) patients in the step-up group and 219 (70%) patients in the step-down group (odds ratio 0.92, 95% CI 0.7-1.3). The average medical costs were lower for patients in the step-up group than for those in the step-down group ((euro)228 vs (euro)245; p=0 . 0008), which was mainly because of costs of medication. One or more adverse drug events were reported by 94 (28%) patients in the step-up and 93 (29%) patients in the step-down group. All were minor events, including (other) dyspeptic symptoms, diarrhoea, constipation, and bad/dry taste. Interpretation Although treatment success with either step-up or step-down treatment is similar, the step-up strategy is more cost effective at 6 months for initial treatment of patients with new onset dyspeptic symptoms in primary care. Funding The Netherlands Organisation for Health Research and Developmen

Early Assessment of Thiopurine Metabolites Identifies Patients at Risk of Thiopurine-Induced Leukopenia in Inflammatory Bowel Disease

BACKGROUND AND AIMS: Only a quarter of thiopurine-induced myelotoxicity in IBD patients is related to TPMT deficiency. We determined the predictive value of 6-thioguanine nucleotide (6TGN) and 6-methylmercaptopurine ribonucleotide (6MMPR) concentrations one week after initiation (T1) for development of leukopenia during the first eight weeks of thiopurine treatment. METHODS: The study was performed in IBD patients starting thiopurine therapy as part of the Dutch randomised controlled TOPIC trial (ClinicalTrials.gov NCT00521950). Blood samples for metabolite measurement were collected at T1. Leukopenia was defined by leukocyte counts <3.0x10*(9)/L. For comparison, patients without leukopenia who completed the eight weeks on stable dose were selected from the first 272 patients of the TOPIC trial. RESULTS: Thirty-two patients with, and 162 patients, without leukopenia were analysed. T1 threshold 6TGN concentrations of 213 pmol/8x10*(8) erythrocytes and 3,525 pmol/8x10*(8) erythrocytes for 6MMPR were defined: patients exceeding these values were at increased leukopenia risk (OR 6.2 (95%CI: 2.8-13.8) and 5.9 (95%CI: 2.7-13.3), respectively). Leukopenia rates were higher in patients treated with mercaptopurine, compared to azathioprine (OR 7.3 (95%CI: 3.1-17.0)), and concurrent anti-TNF therapy (OR 5.1 (95%CI: 1.6-16.4)). Logistic regression analysis of thiopurine type, threshold concentrations, and concurrent anti-TNF therapy revealed that elevations of both T1 6TGN and 6MMPR resulted in the highest risk for leukopenia, followed by exceeding only the T1 6MMPR or 6TGN threshold concentration (AUC 0.84 (95%CI: 0.76-0.92)). CONCLUSIONS: In approximately 80% of patients, leukopenia could be explained by T1 6TGN and/or 6MMPR elevations. Validation of the predictive model is needed before implementing in clinical practice

Patients' beliefs about medicine are associated with early thiopurine discontinuation in patients with inflammatory bowel diseases

BACKGROUND: Patients' beliefs about medicine may either reflect the necessity for treatment or concerns regarding the treatment. We explored the extent to which these beliefs have an effect on thiopurine metabolite levels and premature discontinuation in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Patients enrolled in the 'Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory Bowel Disease Clinics' (TOPIC) trial were asked to complete the Beliefs about Medicine Questionnaire (BMQ) 4 weeks after thiopurine initiation. The BMQ measures perceptions about treatment necessity and concerns. On the basis of the necessity and concern scores, patients can be categorized as accepting, ambivalent, indifferent, or skeptical. The thiopurine discontinuation rates for these belief subgroups were compared by Kaplan-Meier curves. Furthermore, clinical response and metabolite levels were compared between the belief subgroups. RESULTS: A total of 767 patients with IBD started thiopurine treatment, of whom 576 (75%) completed the BMQ. Patients could be classified as accepting (34%), indifferent (17%), ambivalent (34%), or skeptical (15%). Compared with patients in the accepting group (discontinuation rate 22%), patients with an indifferent (35%; P=0.02), ambivalent (37%; P<0.01), or skeptical belief (54%; P<0.01) had higher thiopurine discontinuation rates. No differences were observed in the steady-state thiopurine metabolite levels between the different belief subgroups. CONCLUSION: Patients with a low perceived treatment necessity or high concerns toward IBD treatment were more likely to discontinue thiopurine treatment prematurely. Extra attention toward these patients might prevent premature discontinuation