Impact of detection bias on the risk of gastrointestinal cancer and its subsites in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for gastrointestinal (GI) cancers, but variations in study designs of observational studies may have yielded biased results due to detection bias. Furthermore, differences in risk for GI cancer subsites have not been extensively evaluated. We aimed to determine the risk of GI cancer and its subsites in patients with T2DM and how it is affected by detection bias. METHODS: A matched cohort study was performed using the NCR-PHARMO database. New-users of ≥1 non-insulin anti-diabetic drug during 1998-2011 were matched with non-diabetic controls by year of birth, sex, and time between database entry and index. Cox regression analyses were performed with and without lag-period to estimate hazard ratios (HRs) for GI cancer and its subsites. Covariables included age, sex, use of other drugs and history of hospitalisation. RESULTS: An increased risk of GI cancer was observed in T2DM patients (HR 1.5, 95% confidence interval [CI] 1.3-1.7) compared with controls, which was attenuated in the 1-year lagged analysis (HR 1.4, 95% CI 1.2-1.7). Stratified by subsite, statistically significant increased risks of pancreatic (HR 4.7, 95% CI 3.1-7.2), extrahepatic bile duct (HR 4.2, 95% CI 1.5-11.8) and distal colon cancer (HR 1.5, 95% CI 1.1-2.1) were found, which remained statistically significantly increased in the lagged analysis. CONCLUSIONS: T2DM patients had a 40% increased risk of GI cancer. Increased GI cancer risks tended to be weaker when reducing detection bias by applying a 1-year lag-period. Future observational studies should therefore include sensitivity analyses in which this bias is minimised.

Value judgements that matter to patients remain implicit in oncology guidelines: an observational study.

BACKGROUND: Clinical practice guidelines are often evidence-based. However, it is inevitable that there are value judgements in the practical recommendations contained in the guidelines. In order to see if patients are ultimately being supplied with sufficient information to help them make treatment decision, we determined 1) which value judgements influence the process of developing guidelines for palliative chemotherapy, and 2) whether these value judgements were made explicit in the final guideline report. METHODS: We studied the development process of six Dutch oncology guidelines in which palliative chemotherapy plays a substantial role. We observed the guideline development groups (GDGs), conducted semi-structured interviews with individual GDG members (including the chairs), and analysed the minutes of GDG meetings and subsequent versions of the guidelines. A value judgement was defined as a statement about the value of a patient outcome with regard to palliative chemotherapy. RESULTS: We identified the following value judgements in the process of guideline development: 1) consensus on what should be considered as valuable minimum patient outcomes, 2) preference for tailored treatment in situations where there is no evidence of treatment effect, 3) preference for 'doing something' even when there is sufficient evidence of no effect, and 4) the patient outcome of 'prolonging life'. These value judgements, however, were not reported in the final guideline. CONCLUSION: At least the last two value judgements mentioned are relevant for patients with incurable metastatic cancer in making decisions whether to undergo chemotherapy and what kind. Value judgements should be made explicit in guidelines, so that clinicians can transparently discuss treatment options with individual patients.

Structure of Colorado potato beetle lipophorin: differential scanning calorimetric and small-angle X-ray scattering studies.

The structure of lipophorin, isolated from hemolymph of the Colorado potato beetle, was investigated by differential scanning calorimetry (DSC) and small-angle X-ray scattering. The DSC heating curves of intact lipophorin showed endothermic peaks that were similar to peaks obtained with the hydrocarbon fraction isolated from this lipophorin. The observed peaks correlated with the transition of the hydrocarbons from an ordered into a more disordered state. Changes in structure of the lipophorin particles with increasing temperature were also observed by small-angle X-ray scattering studies. The structural organization of lipophorin was further elucidated by simulation analysis, using a three-layered symmetrical sphere as a model. These studies revealed that lipophorin from the Colorado potato beetle is a sphere with a maximum diameter of 175 A. The sphere is composed of three radially symmetrical layers of different electron densities. The outer layer (37.5-39.5 A in thickness) is composed of phospholipid, apolipophorin I, and part of apolipophorin II. The middle layer (5-10 A) contains diacylglycerol, the rest of apolipophorin II, and probably beta-carotene. The core of the particle (40-45 A) only contains hydrocarbons. This structure differs from another model, previously proposed for cockroach and locust lipophorins [Katagiri, C., Sato, M., & Tanaka N. (1987) J. Biol. Chem. 262, 15857-15861], in the small size of the middle layer. The volume of the middle layer correlated well with the low diacylglycerol content of this lipophorin.